Titania-based generator for AC-225 production

Abstract

In one aspect, the present technology relates to a method for producing Ac, the method comprising the steps of preparing a phosphate-modified titania material to produce an ion exchange material, and reacting the phosphate-modified titania material to produce a Th-loaded titania material. 229 contacting a solution containing Th with the ion exchange material; 225 eluting the Th-loaded titania material with a washing solution to generate an elution solution containing an elution mixture including Ac; 225 concentrating the elution solution to produce an elution mixture containing Ac; 225 and separating Ac.

Description

Detailed description of the invention

[0001] [Related applications] This application claims the benefits of U.S. Provisional Application No. 63 / 177,037, filed on April 20, 2021, and U.S. Provisional Application No. 63 / 284,941, filed on December 1, 2021. These applications are incorporated herein by reference.

[0002] [Introduction] Alpha-emitting radionuclides are promising as radiotherapeutic agents in the treatment of a wide range of malignant tumors. Alpha particles, due to their high energy, can destroy malignant tumors, while their short penetration depth limits damage to surrounding healthy tissue. Of particular interest to medical researchers is actinium (Ac), especially its 225 radioisotope, which is used, for example, in targeted alpha therapy (TAT). 225 It is Ac). 225 The advantages of Ac are that it has an almost ideal half-life of 10 days, and the alpha particle emission range is roughly the same size as a human cell. 225 A ligand may be used to bind Ac to a monoclonal antibody. The monoclonal antibody is pre-programmed to transmit and deliver these alpha-emitting molecules to target affected cells.

[0003] [Titania-based generator for Ac-225 production] In one embodiment, the present technology relates to a method for producing Ac. The method comprises the steps of preparing a phosphate-modified titania material so as to produce an ion-exchange material, and preparing a Th-supported titania material so as to produce a Th-supported titania material using the radioactive isotope of thorium-229. 229 A step of bringing a solution containing Th) into contact with the ion exchange material, 225 A step of eluting the Th-supported titania material using a washing solution so that an elution solution containing an elution mixture including Ac is produced, 225A step of concentrating the elution solution so that an elution mixture containing Ac is produced, and from other radioactive isotopes in the elution mixture 225 The process includes a step of separating Ac.

[0004] In other embodiments of the above-described model, the step of preparing the phosphate-modified titania material includes: mixing titania with a solution so as to produce a diluted titania solution or slurry; stirring the diluted titania solution while maintaining a temperature within a selected range; extracting the phosphate-modified titania from the diluted titania solution by draining the supernatant of the phosphate-modified titania; washing the phosphate-modified titania so as to produce washed phosphate-modified titania; drying the washed phosphate-modified titania so as to produce dried phosphate-modified titania; and collecting the dried phosphate-modified titania. For example, the step of stirring the diluted titania solution may be performed at room temperature or at a temperature of 80°C.

[0005] In another embodiment, the technology relates to a method for separating Ac from an Ra / Ac mixture. The method includes the steps of: concentrating the Ra / Ac mixture in a first solution; passing a first resin through the Ra / Ac mixture; adding a second solution; passing a second resin through the Ra / Ac mixture; and separating Ra from Ac such that separated Ra and separated Ac are produced.

[0006] In yet another embodiment, the technology relates to an Ac generation generator. The Ac generation generator comprises a first part of the generator, a first fluid valve in the first part of the generator, a column body including an internal chamber, a second part of the generator, and a second fluid valve in the second part of the generator. In another embodiment, the Ac generation generator may include a quartz column configuration that does not have the first fluid valve and / or the second fluid valve, for example, using a U-tube instead of a valve for access to a Th-supported medium.

[0007] In one embodiment, the present invention relates to a system for separating Ra and Ac from an Ra / Ac mixture. The system comprises: a first separation column comprising a first resin and a second resin in separate portions of a first internal chamber of the first separation column, and including a sealable first access port configured to allow the addition and removal of the Ra / Ac mixture and the first resin; and a second separation column comprising a plurality of first resins in separate portions of a second internal chamber of the second separation column, and including a sealable second access port configured to allow the addition and removal of Ra residue, Ac residue, or the second resin.

[0008] In yet another aspect, the present technology relates to an Ac generator. The Ac generator includes a first part of the generator, a first fluid valve in the first part of the generator, a column body including an internal chamber, a second part of the generator, a second fluid valve in the second part of the generator, a first separation column including a first resin and a second resin in separate parts of a first internal chamber of the first separation column, and a sealable first access port configured to add and remove a Ra / Ac mixture and the first resin, and a second separation column including a plurality of first resins in separate parts of a second internal chamber of the second separation column, and a sealable second access port configured to add and remove a dried Ra residue, a dried Ac residue, or the second resin.

[0009] In a further aspect, the present technology relates to a method of buffering a contact solution within a column of an Ac generator. The method includes circulating a preconditioning solution within the column at a predetermined circulation rate for a predetermined duration, supplying a Th substance into the column at a predetermined supply rate after the circulating step, and washing the loaded Th substance at a predetermined washing rate.

[0010] [Brief Description of the Drawings] The following drawings, which form a part of this application, illustrate the described technology and are not intended to limit in any way the scope of the claimed invention. The scope of the claimed invention is to be based on the claims appended to this application.

[0011] FIG. 1 is 233 a schematic diagram of the decay chain from 229 U to

[0012] Figure 2 is a schematic diagram of the process flow for Ac production according to various embodiments of this disclosure.

[0013] Figure 3 shows 232 This plot shows the chain reaction of Th's collapse.

[0014] Figure 4 shows the reception of nanoporous TiO2 by various embodiments of this disclosure. 4+ This plot shows how the uptake distribution coefficient changes with pH.

[0015] Figures 5 to 13 are plots of the change in Th concentration with respect to elution amount for various embodiments of this disclosure.

[0016] Figure 14 shows several SEM images of surface-modified TiO2 materials according to various embodiments of this disclosure.

[0017] Figures 15A to 15D are SEM images of TiO2 starting materials and synthesized materials according to various principles of this disclosure.

[0018] Figure 16 shows various embodiments of the present disclosure of Th by TiO2 and surface-modified TiO2. 4+ This plot shows how the uptake distribution coefficient changes with pH.

[0019] Figures 17 to 19 illustrate various embodiments of the present disclosure. 228 Ra and 228 This plot shows the radioactivity and recovery rate of Ac.

[0020] Figure 20 shows the various embodiments of this disclosure in relation to Th supply. 228 Ra and 228 This is a schematic diagram of the elution behavior of Ac.

[0021] Figures 21 and 22 are exemplary elution graphs at Th saturation according to various embodiments of this disclosure.

[0022] Figure 23 shows an example of a method, according to various embodiments of this disclosure, for reducing Ra sorption onto IX material in a column and thereby increasing the recovery rate of Ra.

[0023] Figure 24 shows an example of a generator in the form of a column packed with IX material.

[0024] Figure 25 shows another example of a generator in the form of a column packed with IX material.

[0025] Figure 26 is a flowchart showing methods for generating Ac according to various embodiments of this disclosure.

[0026] Figure 27 is a flowchart showing methods for preparing phosphate-modified titania materials according to various embodiments of this disclosure.

[0027] [Detailed explanation] In one embodiment, the present technology relates to a method for generating Ac. The method comprises the steps of preparing a phosphate-modified titania material so as to generate an ion exchange material, and so as to generate a Th-supported titania material. 229 A step of bringing a solution containing Th into contact with the ion exchange material, 225 A step of eluting the Th-supported titania material using a washing solution so that an elution solution containing an elution mixture including Ac is produced, 225 A step of concentrating the elution solution so that a concentrated mixture containing Ac is obtained, and from the elution mixture 225 The technology includes a step of separating Ac. In another embodiment, the technology relates to a method for separating Ac from chemical impurities and radionuclide impurities.

[0028] Currently, 225 Ac is produced by irradiating thorium metal with proton beams. 232 When thorium metal containing Th is irradiated, more than 700 different isotopes, which are of potential interest, are produced. 225 It collapses into Ac 225A product containing Ra can be obtained. After proton beam irradiation, the desired radionuclide can be recovered by dissolving the irradiated thorium in an acidic solution. Desired actinium and radium products can be separated from thorium starting materials and other spallation products using various chromatography techniques.

[0029] 232 Irradiation of th metals produces, in addition to actinium and radium, a considerable amount of undesirable radioisotopes compared to the desired radionuclide products. For example, radioisotopes of lower lanthanide elements (e.g., lanthanum and cerium) are undesirable in the preparation of radioisotopes intended for medical use. Furthermore, 232 As another undesirable radioactive isotope formed by Th irradiation 227 Ac exists, and this isotope 225 Because it is very difficult to separate from Ac, 225 Ac almost always contains a certain amount 227 Ac is introduced. Thus, the formation of radioactive isotopes, such as lower lanthanides, is undesirable. Therefore, removing such undesirable radioactive isotopes can be advantageous.

[0030] The principles of this disclosure include, for example, a different isotope of Th ( 229 Th) 225 This includes systems and methods for generating Ac. In various embodiments, 225 Ac is 229 It is generated from Th. 229 Th is 233 It originates from U. Furthermore, 225 Ac products contain 227 isotopes 229 Because it does not exist in the Th collapse chain, 227 It essentially has no Ac. 233 From U 229 As shown in Figure 1, which is a schematic diagram of the decay chain of Th and subsequent daughter nuclides, 229 Due to the natural decay of Th225 Ra is generated, 225 Ra is 225 It undergoes beta decay into Ac. As shown in the diagram, 233 U has a half-life of 160,000 years. 229 It collapses into Th. 229 Th has a half-life of 7800 years. 225 It collapses into Ra. 225 Ra has a half-life of 14.9 days. 225 It collapses into Ac. 225 Ac has a half-life of 10 days. Because these half-lives are relatively short, 225 Ra and 225 Ac is 229 It can be harvested regularly from Th.

[0031] In various embodiments of the method described herein, 229 A storage solution containing Th isotopes and their progenies can be brought into contact with an ion-exchange (IX) material. The IX material is 229 It is configured to selectively capture Th and selectively reject its daughter nuclides (e.g., Ra and Ac). These daughter nuclides may remain in the contact storage solution. In the systems and methods described herein, the IX material is 229 Porous titania (TiO2) may be maintained or modified under conditions that promote selective capture of Th, or may contain porous titania (TiO2). Accordingly, the exemplary systems and methods described herein are derived from the feedstock solution. 229 This invention demonstrates a configuration that allows for easier separation of Th from its daughter nuclides and immobilization on a capture platform. 229 By simply eluting the Th-supported IX material with a washing solution, without requiring comprehensive pre-treatment or post-treatment steps, 225 Ac can be harvested regularly. By using IX material in the column configuration (morphology), a robust, easily scalable, and reproducible approach (method) becomes possible without large variations in operating parameters.

[0032] Figure 2 shows an example of a process flow 200 for Ac generation according to various embodiments of the present disclosure. For example, flow 200 may include at least the following steps:

[0033] (After uranium separation) 229 The process involves passing the Th preservation solution through an IX generator column to capture Th on the IX material and perform Ra / Ac elution (shown as Step 1 in Figure 2); passing the residual Th preservation solution through UTEVA (Uranium and Tetravalent Actinides) resin, or other Th recovery routes as needed (shown as Step 2); eluting the IX material with an elution washing solution to remove the desired Ac from the IX generator column, and evaporating the elution solution to concentrate the contained eluted daughter nuclides (shown as Step 3); and separating Ac from Ra and other eluted daughter nuclides to obtain a purified Ac solution for use in pharmaceutical products for targeted alpha-ray therapy (shown as Step 4 in Figure 2).

[0034] Step 1: Step 1 is a supply operation. This supply operation involves applying selective IX material to 229 This may involve multiple operations designed to supply Th. After loading, 229 Th then disintegrated over time, 225Daughter nuclide products containing Ac are produced. In the embodiments described herein, the ion exchange material includes a titania material such as TiO2 or porous TiO2. In yet another embodiment, the titania material is modified with phosphorus by mixing the titania material with an H3PO4 solution (e.g., a 1 M H3PO4 solution). Furthermore, the mixing of the titania material and the H3PO4 solution may be carried out at room temperature for 16 to 45 hours. Alternatively, the mixing of the titania material and the H3PO4 solution may be carried out at a temperature of up to 80°C for about 5 hours. For example, a thorium-containing preservation solution 210 is brought into contact with the ion exchange material in the column 230. In another embodiment, a thorium-containing preservation solution is brought into contact with a phosphorus-modified titania material (e.g., phosphorus-modified TiO2 or phosphorus-modified porous TiO2) in the column 230. In another embodiment, the Th preservation solution may contain one or more of the following: NaNO3, HOA (acetic acid), NaOA (sodium acetate), and HNO3 (nitric acid). In another embodiment, column 230 contains titania material. In addition to the durations and temperatures discussed herein, other durations and temperatures may be applied. For example, the step of mixing the titania material with the H3PO4 solution may be carried out at a temperature in the range of 1 to 100°C (e.g., 10 to 90°C, 10 to 30°C, or 70 to 90°C). In other embodiments, the duration of the step of mixing the titania material with the H3PO4 solution may be in the range of 0.1 to 100 hours (e.g., 5 to 50 hours, or 10 to 40 hours).

[0035] Column 230, as Th decays over time, 225Because Ac is produced, it may be referred to as a “generator” column, an “actinium generator” column, an “actinium generator,” or simply “generator” 230. Although referred to herein as a “column,” the generator 230 may have any shape, including, for example, a capsule (spherical cylindrical), cylindrical, spherical, conical, pyramidal, frustoconical, or frustoconical shape. In one embodiment, the column 230 is a sealable container that contains the IX material (and the supported thorium) and allows the IX material to be washed with an eluent without loss of the IX material. Further embodiments of the column 230 are described in more detail below.

[0036] Before contact in column 230, the thorium-containing storage solution may be dried in the evaporator 220 to increase the thorium concentration. In another embodiment, the flow rate of the thorium-containing solution in column 230 when contacting the titania material is in the range of 2 to 10 mL / h. In yet another embodiment, 229 At least a portion of Th is sorbed onto the titania material inside column 230.

[0037] After supporting thorium on the IX material in column 230, the IX material in the column can be washed with a solution according to step 3 described later. Ac that has accumulated in column 230 over time since the previous wash is removed by the next washing step, so the washing process is sometimes referred to as "milking" of the generator 230.

[0038] Step 2: Step 2 is a thorium recovery operation. This thorium recovery operation ensures that the amount of thorium lost from the system is kept to a minimum. This recovery operation may include a series of operations designed to recover any Th material that was not successfully captured onto the IX material during the feeding operation. In one embodiment of Step 2, the contact storage solution obtained from column 230 after contact with the phosphate-modified titania material is dried and then passed through a resin (e.g., UTEVA resin 250). After passing through UTEVA resin 250, thorium is eluted and recovered. Drying can be carried out using any known method or apparatus. In the embodiment shown in Figure 2, drying is carried out in an evaporator 240.

[0039] Step 3: Step 3 is a milking operation. In this milking operation, Ac is washed out and collected from the IX material in the column. Alternatively, this washing may be called elution, and the solution used for washing may be called an eluate. The milking operation may be performed periodically on a schedule or at random intervals, depending on the need for Ac. In the illustrated embodiment, the milking operation includes several operations designed to recover Ac and Ra materials, since Ra is also produced in column 230 and Ra itself may have value. Step 3 is a daughter nuclide product of thorium. 225 and 225 The washing solution is passed through the column to produce a solution containing Ra. The rate at which the washing solution passes through the column 230 may be controlled to affect the amount of Ac and Ra obtained during a particular washing operation. For example, in one embodiment, the elution rate of the washing solution is in the range of 30 to 60 mL / h. Various eluents may be used. In another embodiment, the eluent includes, for example, an HOA / NaOA solution.

[0040] Step 4: Step 4 is an Ac / Ra separation operation. In this Ac / Ra separation operation, Ra is separated from Ac. In the illustrated embodiment, the separation operation includes several operations designed to separate the Ac substance and the Ra substance. Step 4 involves elution and evaporation. 225 Ac is collected. For example, 225 Ac is, for example, in the concentrated elution mixture. 225 Ac 228 Separated from Ra and then separated from the concentrated elution mixture. 225 Ac is collected by collecting it. In another example, from the concentrated elution mixture 228 Ra may also be separated. In the examples, from the concentrated elution mixture 228 and 228 The recovery rate of at least one of Ra is greater than 96% by weight. Unless otherwise specified or as is clear from the context, when % is used herein, it refers to weight percent.

[0041] In various embodiments, the following experimental results provide examples of various principles of this disclosure.

[0042] (Examples) In the following experiment demonstrating the feasibility of a titania-based AC generator, for safety reasons in some cases, 232 Classical isotopes 229 It can be used as a substitute for the Th isotope. Because their electronic structures are nearly identical, the generator behavior can be reproduced completely or substantially between these two isotopes with little variation.

[0043] (Material synthesis) Porous titania with a phosphate-modified surface may be prepared, and the synthesis conditions are summarized in Table 1A below.

[0044] Sample 1 (TP168-31-1): Mix approximately 1.0 g of titania obtained from Sachtopore with 125 mL of 1.0 M H3PO4 in a beaker. Place the mixture on a stirring plate and stir at 800 rpm for 45 hours at room temperature, then allow the solid to settle for 1 hour. Drain the solution and wash the residue five times with 10 mL of deionized (DI) water. Dry the washed solid by placing it on a hot plate at 100°C for 1 hour. The dried solid is then collected, analyzed, and stored for future sorption experiments. The material is characterized by X-ray diffraction and scanning electron microscopy. The product may remain unchanged even if the process is scaled up fivefold. Although the concentration of H3PO4 described above is equal to 1.0 M, various concentrations of H3PO4 may be used. For example, the concentration of H3PO4 may be within the range of 0.1 M to 10 M (including the ranges of 0.1 to 0.5 M, 0.5 to 1 M, 1 to 5 M, and 5 to 10 M).

[0045] Sample 2 (TP168-31-2): In the modified procedure, the reaction is carried out at a higher temperature. TiO2 (~1.0 g, Sachtopore) and 1.0 M H3PO4 (125 mL) are reacted at 80°C for 5 hours while stirring the mixture at 800 rpm. Then, heating is stopped and stirring is continued for a further 16 hours. The product is collected, washed, and dried according to the same protocol as for the material in Sample 1 (TP168-31-1). The material is characterized by X-ray diffraction and scanning electron microscopy techniques. The product may remain unchanged even when the process is scaled up fivefold. Although the mixing rate is stated to be equal to 800 rpm above, other mixing rates (e.g., in the range of 10 rpm to 2000 rpm) may be used.

[0046] Sample 3 (TP168-32-1): This synthesis followed the same protocol as for the synthesis of Sample 1 (TP168-31-1), except that the stirring time was limited to 21 hours instead of 45 hours. As with the other two samples, the product was characterized using X-ray diffraction and scanning electron microscopy techniques.

[0047] Sample 4 (TP168-36-1): This synthesis followed the same protocol as the synthesis of Sample 2 (TP168-31-2), except that the stirring speed was reduced to 300 rpm.

[0048] [Table 1A]

[0049] In another example, 2.5 ml of 85% H3PO4 was added to 250 ml of DI water in a 500 ml beaker to form a 2.5 M H3PO4 solution. 28.18 g of TiO2 (particle size 110 μm) was added to the beaker and stirred at 420 rpm using an overhead stirrer. The mixture was then heated to an internal temperature of 70°C on a hot plate while stirring. After heating for 6 hours, the mixture was cooled to room temperature and stirred for a further 18 hours. The upper liquid phase was then drained, and the TiO2 slurry was washed four times with 50 ml of DI water. 100 ml of DI water was added to the beaker, the mixture was stirred for 1 hour, then drained, and washed four times with 50 ml of DI water. This stirring-draining-washing cycle was repeated four more times. After the final draining, the beaker was placed on a 160°C hot plate for 1 hour to dry the TiO2. 27.26 g of product was recovered. The results are shown in Table 1B below.

[0050] [Table 1B]

[0051] [Table 1C]

[0052] (Evaluation of material properties) The synthesized materials were characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM). XRD data were collected using a Rigaku MiniFlex benchtop X-ray diffractometer. SEM images were collected using an FEI Quanta instrument.

[0053] (Solubilization experiment) The adsorption experiments consisted of batch contact experiments that evaluated and provided guidance on the conditions and materials necessary to increase or maximize uptake capacity and improve the sorption rate.

[0054] (Batch sorption) The sorbation experiment is performed in a centrifuge tube under ambient temperature (room temperature) and ambient pressure (atmospheric pressure). A weighted amount of sorbent is added to each tube, followed by a Th preservation solution maintained at the desired pH by combining HNO3 and NaOH. The preservation solution is prepared by dissolving solid ThCl4·xH2O (MW=505.978g) in the desired solution. A pH range of 2–4 is used for the experiment. The resulting mixture is shaken for a specified time by placing the centrifuge tube on a horizontal shaker. The tube is then centrifuged to allow the solid to settle, a small amount of the supernatant is withdrawn, and the thorium concentration remaining in the dissolved phase is determined by combining ICP-OES and ICP-MS. The amount of thorium sorbed is given by the distribution coefficient K given by equation [1]. d It is expressed as follows.

[0055]

number

[0056] Here, [Th] initial [Th] is the initial concentration of thorium in the storage solution. finalis the final concentration in the supernatant after contact with the sorbent, M is the mass of the sorbent used, and V is the volume of the contact solution. Chemical analysis is also performed to determine the rate of the sorbent process. In this chemical analysis, the process of withdrawing small amounts of supernatant is periodically repeated for the same solution.

[0057] (column) In column experiments, various configurations are used depending on the column size. Typical column sizes are shown in Table 2 below.

[0058] [Table 2]

[0059] In a typical column run, the desired amount of IX material is mixed with DI H2O and packed into the column. The column is then pre-treated as desired, as described later. Th feedstock is prepared by dissolving ThCl4·xH2O solid in DI H2O or a buffer solution. Subsequently, the pH is adjusted using NaOH solution or HNO3 solution. Both gravity flow and pump flow are used for the column. For pump flow, a mechanical syringe pump operated with J-KEM software is used. The eluate is collected in fractions and analyzed by chemical and radiochemical methods.

[0060] (chemical analysis) Chemical analysis of the eluate and sample solution is performed via ICP-OES and / or ICP-MS to analyze the Th, Ti, and P concentrations in the sample solution. For these measurements, fractions of the sample solution are diluted with 2% HNO3 prior to analysis.

[0061] ICP-OES analysis is performed using a PerkinElmer Optima 8000 ICP-OES instrument. The eluate to be analyzed is diluted with 2% HNO3 so that the final concentration of the element to be analyzed (Th, Ti, or P) does not exceed 100 ppm.

[0062] ICP-MS analysis is performed using an Agilent 7800 Quadrupole ICP / MS (Inductively coupled plasma / mass spectrometer) (Agilent Technologies). Similar to ICP-OES, the eluate to be analyzed is diluted with 2% HNO3 so that the final concentration of the elements to be analyzed does not exceed ~1 ppm.

[0063] (Radiochemical analysis) Radiochemical analysis of the eluate is performed using gamma-ray spectroscopy and alpha-ray spectroscopy. Gamma-ray spectroscopy is not only an effective method for initially evaluating the effectiveness of a generator that separates Th from Ra / Ac daughter nuclides in the feedstock, but also provides a method for evaluating the efficiency of periodic Ra / Ac recovery during each harvest cycle. As described above, 232 Th (half-life 1.4x10 10 years) can be used instead of 229 Th. 232 The decay chain of 228 Th includes 228 Ra (half-life 5.7 years), 228 Ac (half-life 6.1 hours), 224 Th (half-life 1.9 years), 228 Ra (half-life 3.6 days), and a plurality of related isotopes. The isotope 224 Ra and the isotope 225 Ra can be good simulators of 228 Ra in an Ac generator. On the other hand, 225 Ac can be used to simulate the chemical behavior of the 228 Ac product. Isotopes of

[0064] For example, the isotope 232 Th may not emit gamma rays by itself, but is generated through the decay process of 232 Th represented by the following formula [2]. 228Ac isotopes have photopeaks sufficient for analysis by gamma-ray spectroscopy. The associated decay shown in equation [2] is 232 From Th 228 (t) represents the collapse into the 1 / 2 (=1.91 years). The relevant gamma-ray peaks are shown in Table 3 (data is based on the IAEA isotope browser).

[0065] [ka]

[0066] [Table 3]

[0067] Therefore, in the separation time in the sample 232 Th and 228 Ra daughter nuclide and 228 The distribution between Ac daughter nuclides is, 228 It can be determined based on the radioactivity of Ac. The 911.2 keV line is selected for analysis. It is present in the gamma-ray sample. 228 Ac is separated 228 The original amount of Ac and 228 Due to the collapse of Ra 228 This is due to the internal growth (ingrowth) of Ac. Therefore, at any given time 228 The radioactivity of Ac is given by equation [3], based on its growth and decay, 228 Ac initial radioactivity and 228 This relates to the initial radioactivity of Ra.

[0068]

number

[0069] Therefore, we accumulate kinetic information regarding the decay of Th, 232 Th / 228 Ra / 228To carefully determine the Ac ratio, multiple data points must be collected for each sample. Therefore, data is collected immediately after the eluate is collected from the column, and then again at certain time intervals.

[0070] Gamma-ray spectroscopy is performed by loading a 5 mL sample into the gamma-ray detector in the sample holder and setting it to count for 3600 seconds, or until 1000 counts are collected in the region of interest at 911 keV. The collected data is copied from the RPT file and transferred to Excel for processing. The date and time the loaded sample was added to the column is used as the decay start time of actinium and radium. This value is subtracted from the date and time of gamma-ray data collection for each sample to determine how much time has passed since the equilibrium between thorium, radium, and actinium was disrupted. From this, the initial residual amount of actinium and the amount of actinium expected to have grown from within the radium are determined via the decay rate and the growth and decay equations. 228 Ra and 228 The radioactivity value of Ac is determined by least-squares fitting to the experimental data.

[0071] 228 Ra and 228 As can be inferred from the half-lives of Ac's daughter nuclides, gamma-ray spectroscopy is effective in the feedstock. 232 While effective for initial assessment of the separation of Th from its daughter nuclides, it is not equally effective for monitoring the effectiveness of regularly harvesting Ra / Ac from the column. 228 Ra 232 This process is time-consuming because it takes a long time for the Th to evolve into secular equilibrium. Therefore, by alpha-ray spectroscopy, 228 Due to the collapse of Th 224 By directly observing Ra, a second validation will be conducted to evaluate the efficiency of periodic Ra / Ac recovery.

[0072] Alpha-ray spectroscopy provides an effective method for scrutinizing the periodic harvesting of Ra / Ac daughter nuclides. An ideal method for scrutinizing the harvesting efficiency of Ra / Ac daughter nuclides would be to evaluate the efficiency of the process from time t=0 (when Th is loaded onto the column) to the time when the Ra / Ac daughter nuclides are eluted. However, 232 Because the half-life of Th isotopes is extremely long, a reasonable proportion of them remain within their lifetime. 228 Ra / 228 The likelihood of Ac being generated is reduced or eliminated, and therefore, it becomes impossible to directly analyze the efficiency of the harvesting process from these daughter radionuclides. Consequently, indirect methods must be employed.

[0073] Figure 3 shows 232 This plot shows the collapse chain of Th. For example, Figure 3 shows 232 This plot shows the chain reaction of Th's collapse, 228 Th (half-life = 1.9 years) 232 It is one of the decay products related to the Th isotope, and in the supply material, 228 Ra and 228 It is produced along with Ac. During the initial supply of the column, 228 Th 232 While Th is expected to be retained within the column, Ra daughter nuclides and Ac daughter nuclides are expected to elute. 228 Th isotopes 224 It decays into Ra, and because its half-life is relatively short, a sufficient amount can be obtained within a reasonable timeframe of 3-4 weeks. 224 Ra can be accumulated. 224 Ra exhibits clear alpha-ray signs at 5.423 MeV and 5.340 MeV, respectively. This provides an opportunity to study the internal growth behavior of Ra in a regular harvest cycle.

[0074] Alpha-ray spectroscopy is performed on 1 mL samples collected from each elution batch. The 1 mL solution is electroplated and deposited onto a stub. Counting is performed using the ORTEC alpha-ray analysis system.

[0075] (result) (Scoping experiment using pure titania (TiO2)) Before applying any modifications, initial scoping experiments are performed on pure titania to evaluate the sorption behavior of Th onto pure (unmodified) TiO2.

[0076] (Distribution coefficient of TiO2 according to pH (K D )) Figure 4 is a plot showing the change in the distribution coefficient of TiO2 with respect to pH in various embodiments of this disclosure. The determination of the effect of pH on Th sorption by titania for selecting an appropriate pH for the operation is described below. For example, as shown in Figure 4, thorium sorption by titania (TiO2) is measured at four different pH values, namely pH 1, 2, 3, and 4, respectively. In the experiment, the amount of titania was kept constant at 50 mg, while the Th concentration was set to 2.5 x 10⁻⁶. -3 M to 2.5x10 -2 The pH was varied up to M. As shown in Table 4 below, the distribution coefficient K increases as the Th concentration gradually increases with respect to a given pH. d It can be observed from the plot in Figure 4 that it gradually decreases.

[0077] In various examples, as the amount of sorbent is kept constant, the distribution coefficient K gradually increases from 1 to 4 in the storage solution. d The value of increases. The conditions are shown in Table 4, and the trend is shown in Figure 4. Preservation solutions with a pH greater than 4 usually exhibit precipitation of Th as a hydroxide species.

[0078] [Table 4]

[0079] (TiO2 column) In various embodiments, column elution may be performed under systematic changes in various parameters, ranging from elution rate, column dimensions, pH of the Th feedstock, to pretreatment of the column material to make it suitable for improved Th uptake, in order to adjust the column processing conditions to increase uptake capacity and improve sorption rate. The results for various column conditions and Th retention rates are shown in Table 5 below.

[0080] In various embodiments, the pH of TiO2 / Ti-OH, evaluated by monitoring the pH of any contact solution, can fluctuate significantly with small changes in the feedstock pH and the Th concentration in the solution. For example, this may be a result of the interfacial potential of TiO2 directly depending on the relative ratio of the protonated surface hydroxyl groups to their deprotonated forms. Within the pH range of 3–7, the relative ratio of the protonated surface hydroxyl groups to their deprotonated forms can become unclear and easily disturbed by small changes in the solution properties at the solution interface. Furthermore, Th uptake by TiO2 is directly influenced by the relative ratio of the protonated surface hydroxyl groups to their deprotonated forms. Therefore, it may be advantageous to control the pH of the entire column to reduce or eliminate fluctuations in Th uptake that may arise due to uncertainties in solution conditions. Several approaches are suitable for controlling the pH of the entire column by pretreatment of IX materials.

[0081] The pretreatment of TiO2 before its formation in the column can be achieved by pre-contacting the material with a pH-adjusting solution (solutions with a pH of 4–8 may be used). The pH-adjusting contact solution is prepared by adjusting the HNO3 / NH4OH ratio in deionized (DI) water. Pretreatment of TiO2 with these solutions is generally observed to improve uptake capacity, with the exception of pH ~8.

[0082] Another possible alternative is to circulate a pH-adjusting solution through the column for an extended period before passing the Th-supplying material through the column for elution. The column's pH can be monitored by periodically examining aliquots of the eluate. This has also been observed to increase Th retention. However, there are advantages to controlling the elution rate during washing. For example, washing the column at a rate of 30-60 mL / h before Th supply may improve Th uptake, while washing at 108 mL / h may worsen Th retention. This may be because a high washing rate affects the composition of materials within the column (perhaps by stirring and reducing the size of particles), resulting in a negative impact on Th retention.

[0083] Based on the observations of the column, the following conclusions and explanations can be reached.

[0084] When all other parameters remain constant, the Th retention rate from a pH 4 feed is higher than that from a pH 3 feed. This is consistent with batch equilibrium experimental results and further supports the idea that the capture of Th by TiO2 is driven by an inner-sphere reaction mechanism that produces Ti-O-Th bond formation. This may be energetically preferable at higher pH. These results suggest that the Th retention rate is likely Ti-OH / Ti-O - It depends on equilibrium, and the higher the pH, the greater the Ti-O - This indicates that the proportion of the portion increases, leading to a higher Th retention rate.

[0085] However, simply pre-treating the column with a high pH solution and then converting Ti-OH to Ti-O -Substantially complete deprotonation can have adverse effects. For example, pretreatment of the resin with a higher pH solution (pH ~ 8), as reflected in the Th retention behavior of columns 168-16 in Table 5 below, can worsen Th retention. This may be a result of the tendency for Th species to precipitate from the solution by forming aggregates of oxides and hydroxides rather than remaining in the solution. These oxide / hydroxide precipitates are not trapped in the pores of titania, but rather can clog the pores, preventing more Th from being captured. This is related to Ti-OH / Ti-O - This suggests that a delicate balance is required between controlling equilibrium and preventing th precipitation.

[0086] Pretreatment of TiO2 with pH-adjusted solutions between 4 and 6 may improve Th retention compared to untreated TiO2. However, the overall Th retention capacity of these pretreated TiO2s can be subject to drastic and often nonlinear fluctuations depending on feed concentration, small changes in feed pH, or column configuration affecting column bed volume and feed flow rate. Such irregular fluctuations in the behavior of treated TiO2s result from the fact that the interfacial potential of TiO2 in the pH range of 4 to 7 is susceptible to small disturbances in the solution interface properties that can be caused by small changes in pH, solution ionic strength, solution concentration, or physical parameters.

[0087] The following shows that a Th retention rate of 99.6% was obtained using gravity-based elution in a column with a narrow cross-sectional area (column 168-23) with a total elution time of 2.5 mL / h. On the other hand, when the flow rate was increased using a peristaltic pump adjusted to an elution rate of 5 mL / h without changing any other factors, the retention rate decreased to 73.3% (column 168-23 in Table 5 below). This indicates that the rate of Th sorption by TiO2 is slow or moderate.

[0088] [Table 5] JPEG0007894388000011.jpg20169

[0089] According to various examples, one advantageous aspect of the generator's performance is that it can elute Th's Ra / Ac daughter nuclides already present in the feedstock as a result of prior Th decay, while also selectively capturing Th from the feedstock. As described in the experimental items, the amount of captured Th can be monitored by chemical characterization of the eluate by ICP-OES and ICP-MS, while gamma-ray spectroscopy can monitor the eluting Ra and Ac. The gamma-ray spectroscopy results for some of the columns shown in Table 5 are shown in Table 6 below. In these experiments, the sample solution after elution through the column is analyzed by gamma-ray spectroscopy. The cumulative results are: 228 Ac and 228 It shows a recovery rate of >95% for both Ra and Ac. This demonstrates the effectiveness of this generator in effectively separating Th from Ra / Ac.

[0090] As will be discussed in subsequent sections, alpha-ray spectroscopy may be performed to improve the accuracy of the Ra / Ac recovery rate calculation. However, as described in the experimental section, 228 Th decays and a considerable amount 224 Because it takes 3-4 weeks for Ra to accumulate, alpha-ray spectroscopy is limited to certain samples for practical reasons.

[0091] [Table 6]

[0092] To summarize the column results, cumulative column results indicate that controlling the column's pH is advantageous for improving the TiO2 / Ti-OH ratio to increase or maximize Th capture and ensure that Th does not precipitate as an oxide. While the above method can achieve this on a large scale, an improved and consistent method of such control helps ensure the reproducibility of the entire operation and better control the scalability of the method. The remaining experiments were based on titania. 225 Two potential pathways for controlling pH within the Ac generator are investigated.

[0093] One potential pathway for pH control is to use a buffer solution to mitigate pH changes. Another option is to modify the surface with phosphate functionality, which may a) provide a stable interfacial potential over a wide and sufficient pH range, and b) improve sorption rates and uptake capacity.

[0094] (Effects of repeated elution cycles) Figures 5A to 5D illustrate the effect of elution on thorium retention rates based on various principles of this disclosure. In various examples, a phosphate-modified TiO2 column supported with 280 mg of Th-232 was tested to simulate repeated elution cycles over a predicted lifespan of 20 years. For each cycle, 80 ml of pH 4 HNO3 solution was passed through the column at 20 ml / h, and the eluate was collected. Each 12 cycles (960 ml) was combined, which corresponds to approximately one year of elution. 10 ml of sample was withdrawn from each group for analysis by ICP-MS, and the remaining solution was concentrated until dry and redissolved in 20 ml of 2% HNO3 for ICP-MS analysis. Thus, a total of 24 groups were analyzed. After 288 elution cycles, the column was divided into sections, each section was extracted with 1 M HCl, and the amount of absorbed thorium was analyzed. The results were then compared with similar section experiments on a newly supplied column to determine the rate of Th migration within the column during elution cycles. In the examples, dissolution tests shown in Figures 5A and 5B revealed no significant loss of Th during a 20-year equivalent cycle. For example, as shown in Figures 5A and 5B, the total loss of Th was 0.006–0.04 mg (~0.013%). Furthermore, section tests showed no significant migration of Th during the dissolution cycle, as shown in Figures 5C and 5D.

[0095] (Effect of buffer solution) In various examples, setting the pH to approximately 4 allows for balanced incorporation of Th without significant concern about precipitation as an oxide or hydroxide. Therefore, the buffer solution may be selected to be appropriate around this pH value. Thus, an acetic acid (HOA) / sodium acetate (NaOA) buffer solution may be selected because (i) acetic acid has a pKa of 4.2 and is therefore effective in the pH range of 3.6 to 4.4, and (ii) although acetic acid can coordinate with Th, the likelihood of the Th-OA bond interfering with the TiO2 bond is low because the significantly larger number of Ti-O sites takes precedence over the similarity in properties of the Ti-O- and AO- bonding groups.

[0096] To improve column conditions, various parameters are tested, including buffer concentration, feedstock pH, and elution rate. A list of column operation and its various parameters is shown in Table 7 below. In general, the use of HOA / NaOA buffer can significantly improve Th uptake capacity. For feedstock consisting of ~100 mg of Th, the Th retention rate with a column containing ~5 g of TiO2 is in the range of 97.00 to 99.99%.

[0097] [Table 7]

[0098] In various embodiments, to understand the effect of the buffer, uptake in the absence of the buffer may be visualized and compared with uptake in the presence of the buffer. In the absence of the buffer, when Th cations are supplied to the column, the Th cations are replaced by protons of Ti-OH, resulting in Ti-O-Th 3+ H is formed + Ions are released into the contact solution. +When more ions are released near the column, these ions or solvated hydronium ion analogs freely form a positively charged layer adjacent to the surface of the TiO2 layer packed into the column. This can create a large overpotential that adds a thermodynamic barrier to the binding of other Th cations, potentially affecting the overall Th uptake capacity. As a representative example of column operation without a buffer solution, elution data for column operation 166-99 in Table 5 above is shown in Figure 6 (initial Th concentration ~0.043M). In Figure 6, the plot of Th concentration in the eluate as a percentage of the eluate volume is superimposed on the change in pH of the eluate shown in Figure 6. Figure 6 provides indirect evidence for the above effect, as a significant decrease in pH can directly correlate with significant Th leakage. Overall, a Th retention rate of 90% is observed, and the total Th leakage reaches 10%. For example, the eluate may contain 0.05M HNO3. In another example, the eluate may contain HNO3 at a concentration in the range of 0.01~10M.

[0099] In another embodiment, pre-treating the column with 0.1 M acetic acid / sodium acetate buffer and adjusting the solution's pH to 4 significantly inhibits Th leakage, potentially improving the overall Th retention to 97% for nearly the same Th supply concentration (~0.043 M), as in column operation 166-109. This is also reflected in the much smaller pH change when Th is added to the column, as shown in Figure 7. A decrease in pH is still observed after Th addition. This may be a result of the buffering capacity at the concentration used being insufficient to quantitatively mitigate and counteract the pH change during the supply process. This is not unexpected, as at pH=4, only 14% of the total acetate (or 0.014 M of 0.1 M HOA / NaOA) is expected to be in salt form. Assuming that Th capture on the column involves a 1:1 association of Th with Ti-O, many surface sites would be required on TiO2 to capture all 0.043 M Th ions. A buffer concentration of 0.014M is probably too low to have a quantitative effect on all of these sites. This is a possible reason for the 3% leakage, which is small but still quantitative.

[0100] In fact, this can be confirmed by reducing the Th concentration by half while increasing the buffer concentration to 0.25 M HOA / NaOA (column operation 166-111). As a result, in the presence of this buffer, the Th retention rate further improved to 99.99%, and Th leakage was reduced (up to 226 ppb at its peak, see Figure 8). At pH 4.2, 20% of the total acetate species, or 0.05 M of the 0.25 M buffer, is in the form of salts. This should provide sufficient buffering capacity for 0.022 M Th. Furthermore, in the presence of acetate species, the Th cation is stabilized and may not precipitate easily even at pH 4.2. This is probably because the acetate forms a complex with Th, preventing the precipitation of Th as a hydroxide by the acetate.

[0101] (Effect of flow rate) Flow rate can play a certain role in Th uptake, but its effect is significantly smaller than in the absence of buffer. Therefore, a supply rate of 2 mL / h allows for a Th retention rate of >99.99%, but increasing the supply rate to 10 mL / h slightly reduces the retention rate to 99.8%.

[0102] (Column saturation and uptake capacity) To improve the Th / IX ratio to ensure no Th leakage occurs, it is useful to evaluate the total Th uptake capacity of the material. In saturation experiments using TiO2 material, a Th-supplying raw material solution was continuously supplied to the column at 6 ml / h (columns 166-117). This process was continued until significant leakage was observed, at which point the Th concentration in the elution solution matched the Th concentration in the storage solution supplied to the column. Based on this study, the Th-loading capacity of the TiO2 material was determined to be ~50 mg / g Th / TiO2.

[0103] In various examples, after saturation, the column was thoroughly washed with 2000 mL of DI water. A small trace of Th was observed in the eluate up to ~100 mL after leakage. This is presumed to be carryover from leakage. Subsequently, as shown in Figure 9, the Th concentration in the eluate decreased rapidly. Furthermore, as shown in the inset, after the traces of Th carryover from leakage were substantially completely washed away, the Th concentration in the eluate decreased to 100 ppb, as determined by ICP-MS. When the column was further eluted with 1000 mL of DI water, the Th concentration fell well below 100 ppb. This suggests that there was little or no release or leaching of Th from the column. Such a low Th concentration in the eluate indicates that Th was strongly bound to the column, resulting in improved retention. A more detailed study of the leaching behavior will be discussed later.

[0104] The second column was supplied at a flow rate of 2 ml / h until it reached 90% saturation (columns 166-122). Due to the approaching saturation, Th leakage was high at 7.2 ppm. Nevertheless, the overall Th retention rate was 99.95%. Therefore, based on equation [4], 95.1% of Th will remain in the column after 100 separations. 225 After elution 229 A detailed list of Th is shown in Table 11.

[0105]

number

[0106] (Scalability) Based on the quantitative retention of Th by TiO2, the scalability of Th retention was evaluated when both the Th content in the feedstock and the column bed volume were increased by an order of magnitude. Therefore, 1.005 g of Th was dissolved in 500 mL of 0.25 M HOA / NaOA buffer solution and eluted through a column (bed volume = 37 mL) consisting of 51.6 g of TiO2 at a flow rate of 10 mL / h. Figure 11 shows the column behavior regarding the change in Th concentration in the eluate and the pH of the eluate in response to the elution rate. Regarding Th retention, while Th leakage may be below the detection limit of ICP-OES, ICP-MS revealed that the cumulative Th leakage was approximately 5 ppb, and the overall retention rate reached >99.99%. This suggests that, compared to a 5 mL column, larger columns appear to have lower Th leakage and, consequently, higher Th retention. This may be a result of Th being in greater contact with TiO2 due to the larger column dimensions. Compared to the 12 mm diameter of a 5 mL column, the diameter of the scaled-up column is measured to be 26.5 mm. A flow rate of 10 mL / h in a 26.5 mm diameter column corresponds to a flow rate of 2 mL / h in a 12 mm diameter column. Furthermore, in this case, the column length is also almost double that of a 5 mL column (67 mm vs. 33 mm), resulting in double the contact length between Th and the column. These cumulative effects lead to a superior Th retention rate when scaled up.

[0107] (Th stripping / recovery from TIO2 column) TiO2-based IX columns offer a robust and convenient configuration for regular harvesting of Ra and Ac. However, TiO2 materials have been found to be susceptible to radiation over time, and if such materials may need to be phased out, they will be valuable. 229 Stripping techniques may be available to recover Th.

[0108] For example, a typical stripping method may be used on column 166-111 before supplying Th, using 1 M HCl. The stripping process can be relatively simple, induced by HCl elution through the column, as shown in the plot of Th concentration in the stripping solution according to the solution volume in the upper part of Figure 12. This solution can quantitatively strip Th, and it is observed that most of the Th is eluted in the first 15 mL (or ~4 column bed volume). Looking closely at the elution graph, spikes in Th concentration are seen at stripping volumes of 135 mL and 180 mL, respectively, as shown in the lower part of Figure 12. These spikes are the result of two coincidental events in which the column remained in contact with the stripping solution for a longer period compared to the rest of the stripping process. These points are shown in the lower part of Figure 12. This actually suggests that Th release from the column follows a slow desorption rate, even in the presence of a moderately strong stripping solution (e.g., 1 M HCl). Therefore, it would be desirable to increase the contact time between HCl and the TiO2 substrate to promote more efficient and uniform elution of Th species from the column, while simultaneously reducing the total rinse volume. However, such contact time may be improved to limit the solubilization of Ti.

[0109] In various examples, the actual recovery rate is substantially equal to 100.0 ± 0.001%. This suggests that there is no significant loss of Th during the loading (feeding), elution, or stripping processes. In addition to demonstrating the feasibility of this method for quantitative Th recovery, these observations also demonstrate an overall process that maintains a material (mass) balance of Th. Elemental analysis is also performed on the elution solution after stripping of Ti to ensure that there is no visible loss of material in the column; according to ICP-OES, the Ti concentration is maintained at less than 5–17 ppm throughout the column. This small mass loss is expected based on the processing conditions and indicates that no large amount of impurities are mixed into the Th storage solution.

[0110] (Sequential harvesting and recovery of Ac / Ra from the TIO2 column) One aspect of the generator's performance is its ability to periodically harvest and elute the generated Ra / Ac progenitor nuclides from the column. To investigate this, alpha-ray spectroscopy was used. 228 Due to the collapse of Th 224 The accumulation of Ra was examined. Two types of columns loaded with Th were tested for Ac / Ra harvesting. Immediately after loading, the columns were repeatedly washed, and as a result, all daughter radionuclides of Ra and Ac present in the Th feedstock at the time of loading were eluted. As shown in Figure 13, this was confirmed by gamma-ray spectroscopy, showing a ~100% Ra / Ac recovery rate in the washing solution. After washing, the columns were allowed to stand for 3-4 weeks. 228 Due to the decay of Th 224 Ra is accumulated. Then, the column is rinsed and alpha-ray spectroscopy is performed. 224 It will be possible to collect and monitor Ra. Unfortunately, 232 Because Th has a long half-life, in the harvest cycle 228 Ac cannot be detected.

[0111] Column 166-96 was subjected to two harvest cycles, and the column was washed with a 0.25 M HOA / NaOA buffer solution maintained at pH 4 at an elution rate of 60 mL / h. In the first cycle, 95% 225 Ra recovery was observed in 40 mL of eluate (~11 bed volume), and in the second harvest, similar recovery was observed in 60 mL of eluate (~16 bed volume was used). Column 166-101 was subjected to one harvest cycle and eluted at the same elution rate using the same buffer solution. Here, 97% 225 Ra recovery is observed in 60 ml of eluate (~16 bed volume). Elution of >95% of the total bed volume reaches a considerable cumulative solution volume, with the rate of flow being a contributing factor. If a reduction in elution volume is desired to reduce subsequent concentration time, a slower elution rate may be used.

[0112] In various embodiments, Th leakage could also be monitored for all of these columns. The overall leakage concentration was low, corresponding to a loss of less than 0.001% of the total amount of Th supported on the column. Furthermore, the Th concentration rose sharply in columns 166-101 and then decreased during rinsing. This indicates that the release of Th from TiO2 was slow and gradually accumulated over time. No further loss of Th beyond the limit detectable by ICP-MS was observed during prolonged rinsing, indicating a high Th retention rate and low desorption rate in the column.

[0113] (Th retention in columns) As mentioned above, the column may be regularly and extensively rinsed with a buffer solution of pH ~4 every 3-4 weeks after Th supply, and Ra / Ac may be harvested. During this time, the eluate is tested for Th leaching into the eluate to evaluate the effectiveness of Th retention. In any case, the cumulative loss of Th is less than 0.001% of the total amount of Th loaded onto the column. In fact, no Th loss is observed unless the column is treated with a strongly acidic stripping solution (e.g., 1M HCl). This indicates that Th is robustly constructed within the column, resulting in high Th retention and, consequently, a high affinity of Th to TiO2.

[0114] (Effects of phosphate on the surface modification of titania) (Preparation of surface-modified titania) In various embodiments, the surface structure of titania may be modified with phosphate functionality. However, the factors that significantly contribute to the bonding tendency and sorption capacity of TiO2 are determined by its surface charge and pore structure. It is unclear whether surface-modified titania has a detrimental effect on the particle size, porosity, and / or structural integrity of the titania, or otherwise reduces the bonding or chemical affinity of the material. To determine the actual effect of phosphate modification in this system, the following experiments were conducted.

[0115] (Evaluation of material properties) Figure 14 shows several SEM images of surface-modified TiO2 materials from various embodiments of this disclosure. X-ray diffraction analysis of the solids revealed that their diffractions matched a single phase corresponding to the anatase phase of TiO2. SEM observations revealed that the TP168-36-1 material had an average particle size distribution (average diameter ~70-80 μm) similar to the starting TiO2 material, while the other three had smaller particle sizes (average diameter ~5-10 μm) (representative scanning electron microscope images are shown in Figure 14). This is presumed to be a result of reaction conditions involving longer reaction times, thermal activation, and higher stirring rates, which promoted particle stirring and consequently broke down the particles into smaller sizes, and it was observed that stirring rate had a dominant effect in controlling particle size.

[0116] Figures 15A to 15D are SEM images of TiO2 starting materials and synthesized materials using various principles of this disclosure. Figures 15A and 15B show the particle sizes of the starting materials, which vary from 40 μm to 200 μm. This is consistent with the manufacturer's specification of an average size of 110 μm. Figures 15C and 15D show the particle sizes of the synthesized materials, which vary from 50 μm to 170 μm, but no significant fracture is observed.

[0117] (Batch sorption) Figure 16 is a plot showing the change in the distribution coefficient of TiO2 and surface-modified TiO2 with respect to pH for various embodiments of this disclosure. Rate plays a role in the sorption behavior of any sorbent, and the characteristics of a good sorbent are a rapid uptake rate and a slow desorption rate. Therefore, a comparison and contrast between the rate of Th sorption of surface-modified TiO2 materials and the rate of Th sorption of commercially available TiO2 is described below. Each sorbent material of ~50 mg is individually brought into contact with 10 mL of a 2.5 mM Th storage solution at pH ~3, and the uptake rate is monitored. Uniform contact between the sorbent and the Th solution is ensured by uniform shaking of the contact solution, and aliquots are taken periodically to determine the Th content in the supernatant.

[0118] Under these conditions, the uptake rate for unmodified TiO2 may be slow or moderate. 4.6 hours after contact K d The value was ~28, reaching a maximum of 107, and then plateaued at ~110 after 262 hours. On the other hand, surface-modified titania showed a significant improvement in sorption rate, and the sorption rate appeared to be dependent on the particle size. The smaller the particle size, the better the sorption rate. Therefore, TP168-36-1, which has an average particle size that is almost identical to commercially available titania, reached ~60 K after 4 hours of contact. d It showed a value and continued to rise. After 340 hours of monitoring, K d The value reached 340, K d The rate of increase over time was gradually decreasing significantly, although it had not yet reached a plateau. In contrast, the TP168-31-1 composite material with an average particle size of ~5 μm showed the best sorption rate among the materials tested, reaching K after 4.2 hours. d The value reached ~240, and finally, after 330 hours, K d The value gradually decreased to ~610. K d Figure 16 shows an overlay of the temporal variation. In various examples, the P-modified titania material has an average particle size of approximately one of the following: 5–10 μm, 30 μm, and 70–80 μm. In another example, the P-modified titania material has an average particle size in the range of 5–100 μm.

[0119] The significant improvement in the distribution coefficient during the transition from pure TiO2 to phosphate-modified TiO2 suggests the potential of these modified materials as IX resins in Ac generators. Furthermore, monitoring of the supernatant contact solutions after 30 days of contact with the sorbents revealed no new internal generation of Th in the supernatant, suggesting minimal desorption of Th from the composite materials. For subsequent columns, TP168-31-1 and TP168-36-1 were selected. Compared to other sorbents, TP168-31-1 showed a higher K dIt was selected because it is superior. On the other hand, TP168-36-1 has a particle size that is most representative of unmodified TiO2 material, and as a result, physical column operating parameters such as material resistance to flow rate and bed volume are expected to be similar to those of the unmodified material. K of the selected material after 4 hours and 200 hours d The values ​​are shown in Table 8.

[0120] [Table 8]

[0121] (column) Based on the significant improvement in the distribution coefficient of the phosphate-modified TiO2 material, as demonstrated by batch experiments, column replacement may be performed under various variable Th concentration, flow rate, and elution rate parameters. For the reasons mentioned above, column experiments may be performed focusing on the TP168-36-1 and TP168-31-1 materials. The results are shown in Table 9. In general, very good Th uptake was observed uniformly for all columns. The range of Th uptake was 99.253 ± 0.004% in the worst case and improved to 99.999 ± 0.001% in the best case. In this case, Th loss was below the detection limit of the ICP-MS instrument. Therefore, for the TP168-36-1 material, a relatively fast supply of 10 mL / h could result in a retention rate of 99.253% or 0.747% Th leakage (column 168-56), but slowing the supply to 2 mL / h improved the Th retention rate to the point where Th loss was not detected above the ICP-MS detection limit. A Th removal rate of 99.999% corresponds to 99.8% of Th remaining after 200 separation batches, based on the above formula [4] (shown in Table 11). Similar improvements in Th removal and capture were also obtained by increasing the TiO2 / Th ratio or by using a buffer.

[0122] For the TP168-31-1 material, a Th retention rate of >99.999% was obtained even when supplied relatively quickly at 10 mL / h without buffer. This indicates that the slow / moderate rate exhibited by unmodified TiO2 was overcome by the phosphate-modified material, resulting in a faster sorption rate. This supports the batch contact rate results mentioned above. While the volume / mass ratio of unmodified TiO2 or TP168-36-1 is 0.72 mL / g, the TP168-31-1 material has a significantly smaller particle size, resulting in a favorable volume / mass ratio of 1.6 mL / g. This is evident in the fact that TP168-31-1 requires a 10 mL column to accommodate 5 g of material, which is clear from the measurement of a bed volume of approximately 7.7 mL for 5 g of TP168-31-1 compared to 3.7 mL for the same mass of TiO2 or TP168-36-1. Therefore, the improved retention rate with this material is a combination of (i) the increased active surface area of ​​this material allowing Th to contact more effectively, resulting in better uptake, and (ii) the increased volume / mass ratio increasing the contact time between Th and the material, which further contributes to better uptake. For example, in the case of TP168-31-1, due to its small particle size, back pressure can become strong if the elution rate is remarkably fast, potentially leading to mechanical leakage or breakage of the column. Therefore, to safely operate columns using this material without breakage, it is recommended to maintain a flow rate of 5-10 mL / h.

[0123] In summary, phosphate-modified TiO2-based materials exhibit nearly quantitative Th uptake without the presence of a buffer solution and without the need to slow down the Th supply rate, thus demonstrating superior Th uptake capacity and faster Th sorption rates compared to unmodified TiO2. This ability to quantitatively uptake Th without the need for a buffer significantly reduces the post-treatment purification process and facilitates the simplification of the entire Ac generation and recovery process.

[0124] [Table 9]

[0125] (Relationship between Th and Ra / Ac incorporation within a column) Figures 15 to 17 illustrate various embodiments of the present disclosure. 228 Ra and 228 This is a plot showing the radioactivity and recovery rate of Ac. After supplying Th to the column, 232 Th's daughter nuclides, that is 228 Ra and 228 To examine the recovery rate of Ac, gamma-ray spectroscopy is performed on the eluted fraction. For some column operations... 228 Ra and 228 The recovery rate of Ac is shown in Table 10.

[0126] [Table 10]

[0127] As shown in Figure 17, when the total Th concentration in the feedstock is 0.093 g or ~371 Bq for a total of 4.5 g of IX material (column 168-50), >99% 228 The recovery rate of Ac is observed. In particular, 46% 228 Only the recovery rate of Ra is observed, which suggests that the remaining substance is retained within the column. This result is in contrast to the results observed for pure TiO2 (a representative example of column 166-96 shown in Figure 18), and is presumed to be the result of Ra binding to the surface phosphate groups within the column. From this, it is further suggested that phosphate-modified TiO2 has some affinity for Ra, while the almost quantitative recovery of Ac indicates that the resin does not have an affinity for Ac. For example, as shown in Figure 19, when the Th concentration in the feed is approximately doubled to 0.174 g or ~708 Bq (column 168-56), 228 The Ac recovery rate remains almost quantitative at 98%, 228The Ra recovery rate increases to ~70%. This suggests that the affinity of phosphate-modified titania is greater for Th than for Ra. At lower Th concentrations of 371 Bq, there are more surface sites available for Ra to bind. Increasing the Th concentration without increasing the amount of IX resin results in Th occupying more surface sites on the modified titania, leaving fewer sites available for Ra. Therefore, higher concentrations of Ra pass through the column uncaptured and are recovered in greater quantities. Thus, the binding affinity of the resin to Th and its two daughter nuclides, Ra and Ac, follows the trend: Th >> Ra >> Ac. A schematic diagram illustrating the elution behavior of Ra / Ac is shown in Figure 20.

[0128] Figure 20 shows the various embodiments of this disclosure in relation to Th supply. 228 Ra and 228 This is a schematic diagram of the elution behavior of Ac. In one example, the preference that the phosphate-modified IX resin shows for Th compared to both Ra and Ac is expected based on relative charge and charge density. A stable Ac recovery rate of >95% in the eluate is a desirable result. The interaction between Ra and phosphate is not surprising. Ra-PO4 3- The interaction in the application of TAT to bone cancer 223 This is because it forms the basis of Ra's medical applications. In fact, the binding affinity of materials to Ra opens up the possibility of a new generator class where both Th and its daughter nuclide Ra are captured while Ac is eluted. This may reduce or eliminate the need for subsequent Ra / Ac separation steps and simplify the process flow sheet.

[0129] (Capacity to import) Figures 19 and 20 show examples of elution graphs at Th saturation for various embodiments of the present disclosure. A desirable feature of good generator material is a high uptake capacity for Th. A high uptake capacity indicates that Th is pre-concentrated in a moderately small bed volume of column material. This will lead to a high concentration of Ac at elution. In fact, this may lead to a substantial reduction or elimination of the subsequent evaporation step for concentrating the eluted fraction when the uptake capacity is high. Motivated by a higher uptake tendency, faster uptake rate, and slower desorption rate for Th, the uptake capacities of two sets of material, namely TP168-31-1 and TP168-36-1, were studied by saturation experiments (continuations of columns 168-56 and 168-66, respectively). This process consists of repeated cycles of passing a Th-containing storage solution through the column of material and then thoroughly washing it. This process is repeated until the Th concentration in the storage solution that has passed through the column matches the Th concentration to be eluted. This indicates that the column has reached its capacity.

[0130] For both materials, approximately 5.0 g of the total material is used. For the TP168-36-1 material, this corresponds to a column bed volume of approximately 3.5 mL, and for the TP168-31-1 material, it corresponds to a bed volume of approximately 8 mL. The larger bed volume for TP168-31-1 is due to its smaller particle size, resulting in a larger contact surface area per unit mass. Figure 21 shows a typical elution graph for 4.9 g of TP168-36-1 material. Th leakage is plotted as a function of elution volume. As more and more Th is supplied to the column, it is observed that more and more Th leaks out with the eluate until the elution concentration equals the Th concentration in the feed. This increase in leakage is not surprising; as Th saturates the upper layer, more and more Th reaches the lower layer, some of which leaks out due to a moderate sorption rate. Before saturation, it can be expected that significantly slowing down the supply rate will result in significantly less Th leakage. Although not shown in Figure 21, a column using TP168-36-1 material reaches full saturation at 0.524 g of Th. This corresponds to a Th uptake capacity of ~0.107 g per 1.0 g of TP168-36-1. As shown in Figure 22, a similar study conducted with TP168-31-1 showed a Th uptake capacity of >0.140 g per 1.0 g of sorbed material. The above examples show that the Th capacity of TP168-36-1 material is twice that of TiO2, and the Th capacity of TP168-31-1 material is more than three times that of pure TiO2.

[0131] (Leaching of Ac and Ra, and subsequent harvesting of Ra) As mentioned earlier, one of the selection criteria for a generator is the recovery efficiency of the generated Ra / Ac daughter nuclides from the column. An effective way to examine the recovery efficiency of these daughter nuclides is through alpha-ray spectroscopy. 228 Due to the collapse of Th 224The objective is to carefully examine the accumulation of Ra. As shown above, in the case of phosphate modifiers, sorption of Ra by the phosphate modifier is observed. Therefore, to avoid complexity, we use Th-saturated columns 168-56 and 168-66.

[0132] As mentioned earlier, column 168-56 is packed with 4.9 g of TP168-36-1. The size and density of TP168-36-1 are similar to those of unmodified TiO2, and the bed volume corresponds to 3.7 mL. 224 To investigate the recovery rate of Ra, the column was eluted 20 days after the initial Th supply using an aqueous solution adjusted to pH 4. An elution rate of 30 mL / h was used. In 10 mL of eluate, a total of 95% was recovered. 225 Ra recovery is observed, corresponding to a bed volume of ~3. This indicates a significant decrease in elution volume compared to unmodified TiO2. This is likely because Th is pre-concentrated within a smaller mass / volume of the sorber due to the higher affinity of the modifying material. For example, Th is not detected in alpha spectroscopy. This indicates that Th is efficiently retained, resulting in no leakage of Th from the column.

[0133] On the other hand, column 168-66 is packed with 4.9 g of TP168-31-1. With the TP168-31-1 material, the volume / mass ratio is considerably higher, and the floor volume is 8.1 mL. 224 To investigate the recovery rate of Ra, the column was eluted with an aqueous solution adjusted to pH 4 21 days after the initial Th supply. An elution rate of 30 mL / h was used. In 20 mL of eluate, a total of 95% was recovered. 225 Ra recovery was observed, corresponding to a bed volume of approximately 2.5. As with the TP168-36-1 material, no Th leakage from the column was detected.

[0134] (Th retention and P loss within the column) Similar to the case of TiO2-based IX resin, a similarly high Th retention rate was observed in the phosphate-modified column. As with the TiO2-based IX resin, the phosphate column, after Th supply, was regularly and extensively rinsed every 3-4 weeks with a pH solution of ~4, and Ra / Ac was harvested. During this time, the eluate was also tested for Th leaching into the eluate to evaluate the effectiveness of Th retention. In each of these cases, the cumulative Th loss was less than 0.001% of the total Th load on the column. This indicates a high Th retention rate and, consequently, a high affinity of Th to the phosphate-based resin.

[0135] In an additional set of experiments, the amount of P released from the column during each of the elution and washing steps was evaluated. To reduce or eliminate and limit P loss, the column was extensively washed with a pH 4 solution before loading Th onto the phosphate modifier after packing. Before supplying Th, a considerable amount of P was observed in the eluate during the initial stages of washing, but it was observed to rapidly decrease to less than ~50 ppm within a bed volume of 5–7. Subsequently, no significant P loss was observed during both the Th washing and the subsequent Ra / Ac elution cycle, with P at its maximum of <10 ppm. It is expected that more vigorous washing of the column before supplying Th may further reduce P loss.

[0136] (Considerations for column design of phosphate-based materials) Compared to unmodified TiO2, phosphate-modified titania exhibits superior Th uptake capacity, faster Th sorption rates, and improved Th retention. Among the tested materials, TP168-31-1, in particular, possesses the fastest Th sorption rate and the highest Th uptake capacity. However, this material has a significant size difference compared to unmodified TiO2; therefore, its surface area / mass ratio is considerably larger than that of TiO2. Consequently, for the same mass of sorbent, twice the column volume required for TiO2 is necessary. On the other hand, the TP168-36-1 material also shows considerable improvement compared to unmodified TiO2, though not to the same extent as TP168-31-1. Because this material has similar particle size and density to unmodified TiO2, it can be used in the same column configurations as TiO2.

[0137] (Experimental conclusion) The overall objective of this study is to test the feasibility of TiO2 and phosphate-modified TiO2 inorganic ion exchange resins constructed in a column configuration for (i) quantitatively acquiring Th from feedstock and separating Th from its daughter nuclides, and (ii) secondly, for immobilizing and retaining Th for long periods so that Ra / Ac daughter nuclides can be harvested periodically.

[0138] In various examples, untreated TiO2 was demonstrated to exhibit moderate Th uptake capacity and slow Th sorption rates. However, pretreatment of TiO2 by either (i) treatment with an HOA / NaOA buffer solution or (ii) modification of the TiO2 surface with highly affinity phosphate groups significantly improved the uptake capacity. Furthermore, surface functionalization of TiO2 with phosphates slowed the desorption rate while significantly improving the sorption rate.

[0139] As demonstrated by periodic rinsing of the Th-supported column, these materials generally exhibit high Th retention rates, with little to no Th leaching even when using an eluent. Th loss per generation cycle is less than 0.01%. Meanwhile, daughter nuclides of Ac and Ra increase periodically and can be easily harvested from the column. This indicates that this is an ideal configuration for an Ac generator. Furthermore, it has been shown that Th can be quantitatively recovered by intentionally stripping the column with a moderately concentrated acidic solution. This indicates that the Th mass balance is maintained even during column operation.

[0140] Therefore, in various examples, both TiO2 and phosphate-modified TiO2 are materials, 225 It provides an improved generator option for Ac, delivering all the necessary qualities desired in a generator.

[0141] In one embodiment, a column configuration employing either unmodified TiO2 with a buffer solution or phosphate-modified TiO2 without a buffer solution was consistently shown to have a Th capture rate of ~100% from the feedstock.

[0142] Furthermore, 99.999% retention of Th was observed, and no mass loss of Th was observed even after multiple washing and elution cycles across multiple column batches. This indicates strong Th affinity and low desorption rate.

[0143] In another example, it was demonstrated that 100% of the Th could be recovered by intentionally stripping the column with a 1M HCl solution after Th supply.

[0144] In a further embodiment, as given in the above formula [2] and shown in Table 11 below, the material balance and recovery rate of Th exceeding 99.99% 225 This could be a determinant of the long-term success rate of an Ac generator.

[0145] Phosphate-modified titania offers further advantages compared to unmodified TiO2, including improved Th capture capacity without the need for buffering (e.g., more than three times the capture capacity). This improved capture capacity means that Th is pre-concentrated within a smaller column bed volume, resulting in a smaller amount of eluate required during Ac elution. This, combined with the reduced or elimination of buffer requirements, simplifies the overall process by reducing the concentration and purification steps after Ac elution.

[0146] The slow / moderate Th sorption rate of unmodified TiO2 can be overcome by surface phosphate modification. In the latter case, the effect is not significantly observed even when the supply rate is increased from 2 mL / h to 10 mL / h, suggesting a significant improvement in the sorption rate. This is likely because, compared to the oxide binder in unmodified TiO2, PO4 3- This is because of its high affinity for Th.

[0147] This column configuration provides a format that suits operational flexibility; thereby enabling a configuration in which Th can be immobilized and subjected to periodic washing for Ac recovery without the need for complicated and time-consuming pre-treatment or post-treatment steps.

[0148] [Table 11]

[0149] According to various examples, phosphate-modified TiO2-based materials exhibit nearly quantitative Th uptake without the presence of a buffer solution and without the need to slow down the Th supply rate. Therefore, they show superior Th uptake capacity and faster Th sorption rates compared to unmodified TiO2. This ability to quantitatively uptake Th without the need for a buffer significantly reduces the post-treatment purification process and facilitates the simplification of the entire Ac generation and recovery process.

[0150] (Treatment to reduce Ra sorption on IX material) Figure 23 shows an example of a method for reducing Ra sorption onto the IX material in a column and thereby increasing Ra recovery, according to various embodiments of this disclosure. In the illustrated example, Th is supplied to the column by passing a Th-supplying material through a column containing the IX material. Although shown as phosphate-modified titania in Figure 23, the IX material may be any one of the phosphate-modified titania, buffered titania, or unmodified titania described above, or a combination of two or more of these IX materials.

[0151] After supporting Th on the column, tetravalent M 4+ Cational salt (M 4+ A prime example of this is Ti 4+ and Zr 4+ The secondary solution of ) will be passed through the column. As a result, a sufficient concentration of M will be obtained. 4+ If it is passed through the column, Th 4+ These ions will fill the empty sites on the column that are not occupied by other ions. The use of tetravalent metal ions provides a means for separation from Ra and Ac, as well as purification from Th. Excess M that elutes without being sorbed on the column 4+ The ions will be captured by the UTEVA column.

[0152] As a result of this entire process, the capture sites on the column are occupied. Therefore, Ra, which is produced along with Ac when Th decays, does not have any available sites on the column and passes through.

[0153] (Column design suitable for use as an Ac generator) Figure 24 shows an example of a generator in the form of a column filled with IX material. The generator 2400 includes a cylindrical column body 2402 defining an internal cavity, a top or lid portion 2404 sealing the cavity when engaged, and a bottom portion 2406 defining an internal chamber 2414 containing the raw material (i.e., IX material in any of the forms described above). One or both of the top portion 2404 and the bottom portion 2406 may be detachably attached to the body 2402 so that the raw material can be inserted into or removed from the generator 2400. This may be achieved by any known system (e.g., corresponding threaded portions (not shown) on the lid portion and inside the cylindrical body). Alternatively, the generator 2400 may be a standalone structure, and the raw material may be loaded through a sealable access port (not shown) or when the generator is constructed.

[0154] In the embodiment shown in Figure 24, two fluid flow valves 2408 and 2410 are provided. The first valve 2408 (which may be an output value in some examples) is located at the top 2404, and the second valve 2410 (which may be an input valve in some examples) is located at the bottom 2406. In yet another embodiment, the generator may not be completely sealed when the lid is engaged, for example, to allow gas to flow out or to allow the generator to be immersed in the extracting material rather than allowing the extracting material to be injected into the generator through a valve or access port. Although valves 2408 and 2410 are shown at the top and bottom of the generator 2400, respectively, those skilled in the art will recognize that valves 2408 and 2410 can be placed in any suitable position and / or orientation and do not necessarily have to be on opposite sides of the generator. Similarly, instead of the simple top and bottom configuration shown, any type, shape or number of valves, U-tubes or openings may be used for the access port. For example, one valve 2408 or additional valves (not shown) may be used as an access port for input (inflow), output (outflow), or redundancy, and / or as a safety measure for the extracted material and / or the generator. In a simple configuration, the generator 2400 may have only one access port, such as a bottle or beaker.

[0155] The generator 2400 may have any shape both outside and inside the raw material chamber. For example, the generator 2400 may take any shape, including, to name just a few examples, the illustrated capsule (spherical cylinder), cylindrical, spherical, conical, pyramidal, frustoconical, or frustoconical shapes.

[0156] Any number, type, and configuration of access ports, valves, shackles, connectors, contact points, or other auxiliary components may be used as desired. For example, in the illustrated embodiment, a diffuser 2412 is provided so that the generator can be easily used as a fluidized bed reactor or packed bed contact reactor. In this embodiment, the diffuser is in the form of a perforated plate with perforations of a size that prevents or reduces the passage of the feedstock material (e.g., particulate matter). However, the solvent introduced from the bottom valve 2410 easily passes through the diffuser 2412 and comes into contact with the feedstock material. This is just one example of the auxiliary components that may be provided on the generator. Many different fluidized bed reactor designs can be incorporated into a generator with additional auxiliary components, such as additional diffusers, manifolds, baffles for evenly distributing the solvent flow, a feedstock chamber / cavity 2414 with a non-cylindrical internal shape, and baffles for directing the flow.

[0157] The generator may be constructed to include openings that facilitate the insertion and removal of a certain physical form of raw material to be used. For example, if one or more large chunks of raw material are used as described above, the generator may be provided with relatively large openings that allow for the insertion and removal of those chunks. This would allow the generator to be reused after the raw material has been used up. Alternatively, the generator may be configured around the raw material with the intention that the raw material be disposed of together with the generator, eliminating the need to remove the raw material from the generator once it has been sufficiently used up, and allowing for waste and / or waste disposal.

[0158] Figure 25 shows 225 Ra(t 1 / 2 (14.9 days) 225 Act(t 1 / 2 Another embodiment of a separation system and separation method for separating from (=9.92 days) is shown. As shown in Figure 25, this system includes, 225For the purification of Ac, an ion chromatography section 2520 is used. In the ion chromatography section 2520, a chromatographic resin (e.g., UTEVA resin or Eichrom resin) is used in the first column 2510, and a rare earth resin is used in the second column 2530.

[0159] For example, 225 Ra and 225 Ac may be dried and dissolved in 4M HNO3, or diluted to 4M HNO3, and then passed through the ion chromatography section 2520. For example, the solution may be passed through UTEVA resin 2510, and then through rare earth (RE) resin 2530. For example, 225 Ra material and 225 The Ac substance may be dissolved in a solution of HNO3 (e.g., 0.05 M HNO3) after passing through UTEVA resin 2510. In various examples, after being dissolved in a solution of HNO3, it is diluted. 225 Ra material and 225 The Ac substance may be passed through the RE resin 2530. In the RE resin 2530, 225 Ac is deposited on RE resin 2530, 225 Ac substance 2540 can be produced, residual amount 225 Ra2545 may be produced. Although resin 2530 is described as RE resin, it may also be DGA resin.

[0160] In ion chromatography section 2520, 225 Ra and 225 Ac can form anions with nitrates and be sorbed onto column 2520. For example, 225 Ra substance 2545 is 225 The solution may be diluted in 4M HNO3 to separate Ra. 225 Ra and 225 Ac can be eluted and separated within the space of column 2520. 225Ra passes through ion chromatography section 2520 along with the initial 4M HNO3, 225 Ac remains on the RE resin 2530. Although the above example describes a 4M HNO3 solution, other concentrations of HNO3 may be used, such as concentrations within the range of 0.1 to 10M HNO3.

[0161] In several examples, then from ion chromatography section 2520 225 To remove Ac, use 0.05M HNO3 from the RE resin. 225 The Ac substance 2540 may be rinsed off. Then the collected 225 The Ac was dried and dissolved in 6M HNO3, and the final product was... 225 The solution may be purified by passing it through three UTEVA resin columns 2560 in the polishing section 2570 so that Ac2580 is produced. 225 Ac2580 may be dried. Although the above examples describe a 0.05 M HNO3 solution, other concentrations of HNO3 (for example, HNO3 concentrations in the range of 0.01 to 10 M) may be used.

[0162] In various examples, separated 225 Rinse Ra2540 in 4M HNO3, 225 It will disintegrate into Ac, as described above. 225 The process of separating and purifying Ac may be repeated. It is conceivable that this method may be modified using other resins having similar properties. Furthermore, depending on the embodiment, more or fewer columns may be used, or columns may be used in combination. For example, in one alternative embodiment, the polishing section 2570 is a single column having three sections of UTEVA resin, rather than three separate columns 2560. Similarly, in one alternative embodiment, the ion chromatography section 2520 is a single column with UTEVA resin on top of RE resin, rather than two separate columns 2510 and 2530.

[0163] In various embodiments, 225 Ac generation may be carried out by using a precipitate of thorium hydroxide or thorium peroxide as a starting material, instead of using thorium on the IX material as described above. In a solution with a pH of about 5, the solubility of thorium hydroxide is low, but Ra and Ac remain in the dissolved phase. In the case of thorium peroxide, the pH is preferably equal to about 1.5. In one example, the thorium precipitate may be rinsed out, and the collected rinse solution may contain Ra, Ac, and trace amounts of Th. The solution may then be dried and dissolved in 8M HNO3. 225 Similar to the Ac separation system 2500, the solution is passed through an anion exchange resin to remove trace amounts of Th, and Ra and 225 Ac may pass through resins 2510 and 2530. Then, with respect to Figure 25, the chromatography method described above is used. 225 Ac may be separated from Ra and purified.

[0164] Figure 26 is a flowchart illustrating a method for producing Ac according to various embodiments of the present disclosure. In Figure 26, method 2600 comprises a series of operations 2610-2650 according to various principles of the present disclosure. In operation 2610, a phosphate-modified titania material (e.g., TiO2) is prepared. Operation 2610 is described in more detail below with reference to Figure 27.

[0165] In operation 2620, the thorium-containing storage solution is brought into contact with an ion exchange material. For example, the ion exchange material includes a titania material such as TiO2 or porous TiO2. In another embodiment, the thorium-containing solution is the result of a thorium purification process and includes one or more of the following: NaNO3, HOA, NaOA, and HNO3. In yet another embodiment, the thorium-containing solution is brought into contact with the titania material in a column containing the titania material. In yet another embodiment, the flow rate of the thorium-containing solution in the column when it is brought into contact with the titania material is in the range of 2 to 10 mL / h. In yet another embodiment, 229At least a portion of Th is adsorbed onto the titania material.

[0166] In another embodiment of operation 2620, a thorium-containing solution is brought into contact with a phosphorus-reformed titania material (e.g., phosphorus-reformed TiO2, or phosphorus-reformed porous TiO2, etc.). As a result of operation 2620, a thorium-supported titania material is obtained. Over time, some of the thorium decays into daughter nuclide products, and as a result, 225 Ac is continuously generated. As mentioned above, and without being bound by any particular theory, the generated actinium does not appear to be bonded to titania as its parent thorium was, and is therefore in a form that can be leached from the titania material by a simple washing process.

[0167] In operation 2630, the thorium-supported titania material is 225 Elution is performed using a washing solution to produce an eluate containing Ac. For example, the elution rate of the washing solution is in the range of 30 to 60 mL / h. In another example, the eluate used in operation 2630 includes, for example, an HOA / NaOA solution.

[0168] In operation 2640, the results obtained in operation 2630 225 Elution containing Ac ( 225 The Ac solution (which can also be called Ac solution) is dried, and the eluted mixture (i.e., 225 Ac, and similarly washable 225 Ra) is concentrated. In one embodiment, after evaporation, the concentrated residual solution is passed through a resin (e.g., UTEVA resin) to concentrate the residual thorium (e.g., 229 Th) may be collected. In one embodiment, the Th retention rate after operation 2640 is within the range of 99.253 ± 0.004% or higher.

[0169] In operation 2650, any of the products generated by the elution operation 2630 and the evaporation operation 2650 225 Ac solution is collected. For example, in a concentrated elution mixture 225 From Ra 225Separate Ac and collect the Ac separated from the concentrated elution mixture 225 by collecting the Ac 225 Collect Ac. In another embodiment, operation 2650 also includes the step of collecting Ra separated from the concentrated elution mixture 225 In multiple embodiments, the recovery rate of at least one of Ac or Ra from the concentrated elution mixture is greater than 96% 225 Ac or 225 Ra

[0170] FIG. 27 is a flowchart showing a method for preparing a phosphate-modified titania material according to various embodiments of the present disclosure. In FIG. 27, method 2700 includes operation 2710. In operation 2710, a titania material (e.g., TiO2, etc.) is mixed with a solution to produce a diluted titania solution. The reader is reminded that during the process in a heterogeneous mixture where the solid is in contact with the reactant solution of diluted phosphoric acid, the titania remains solid and the titania itself does not actually dissolve. The diluted titania solution is also referred to herein as a slurry. In another embodiment, the titania material may be porous TiO2 or may include porous TiO2. For example, the solution may be H3PO4 or may include H3PO4. In another embodiment, the solution may be H3PO4 at a concentration of 1M or may include H3PO4 at a concentration of 1M. In another embodiment, about 1.0 g of titania is mixed with about 125 ml of the solution

[0171] In various embodiments, operation 2720 includes the step of stirring a diluted titania solution or slurry produced by mixing a titania material and a solution. For example, the diluted titania solution is stirred using, for example, a rotating rod, and the rotating rod rotates at a speed of, for example, 300 rpm or 800 rpm, or a speed within the range of 300 rpm to 800 rpm. In another embodiment, the diluted titania solution is stirred for 5 h, 16 h, 21 h, or 45 h. For example, the diluted titania solution is stirred using, for example, a rotating rod, and the rotating rod rotates at a speed of, for example, 300 rpm or 800 rpm, or a speed within the range of 300 rpm to 800 rpm for 5 h, 16 h, 21 h, or 45 h. In a further embodiment, the diluted titania solution is stirred at room temperature, a temperature of 80 °C, or a temperature within the range of room temperature and 80 °C. In yet another embodiment, the diluted titania solution is stirred using, for example, a rotating rod, and the rotating rod rotates at a speed of, for example, 300 rpm or 800 rpm, or a speed within the range of 300 rpm to 800 rpm for 5 h, 16 h, 21 h, or 45 h at a temperature of 80 °C, or a temperature within the range of room temperature and 80 °C. Although the durations of 5 h, 16 h, 21 h, or 45 h are used above, other durations may also be used. For example, as described above, the duration may be a duration within the range of 5 to 50 h.

[0172] In one embodiment, operation 2730 includes the step of extracting residues from the diluted titania solution or slurry by decanting the residues. For example, in operation 2730, the residues are extracted by allowing the diluted titania solution to settle (to cause precipitation). As another example, the residues are extracted by allowing the diluted titania solution to settle for about 1 hour. Other methods of separating solid titania from the liquid residues are also possible, and any suitable method may be used.

[0173] In another embodiment, operation 2740 includes the step of washing the residue to produce washed phosphate-modified titania. For example, the residue is washed once or multiple times, for example, in deionized water. In another embodiment, the residue is washed once or multiple times, for example, in 10 ml of deionized water, or in an amount of deionized water ranging from 1 to 100 ml.

[0174] In another embodiment, operation 2750 includes the step of drying the washed phosphate-modified titania to produce dried phosphate-modified titania. For example, drying is performed by placing the residue on a heating device (e.g., a hot plate). In another embodiment, drying is performed by placing the residue on a heating device (e.g., a hot plate) at a temperature of, for example, 100°C, or in the range of 50 to 150°C. In yet another embodiment, drying is performed by placing the residue on a heating device (e.g., a hot plate) at, for example, 100°C for 1 hour. In operation 2760, the dried residue is collected. This dried phosphate-modified titania is phosphate-modified titania or contains phosphate-modified titania. If the titania is porous titania, this dried phosphate-modified titania is phosphate-modified porous titania or contains phosphate-modified porous titania.

[0175] Various embodiments of this disclosure may be described by the following clauses.

[0176] 1. A method for producing Ac, A step of preparing a phosphate-modified titania material so that an ion exchange material is generated, To generate thorium-supported ion exchange material and contact solution, 229 A step of bringing a solution containing Th into contact with the ion exchange material, 225 A step of eluting the thorium-supported ion exchange material using a washing solution so that an Ac elution solution is generated, A step of concentrating the elution solution so that an elution mixture is produced, From other radioactive isotopes in the aforementioned elution mixture 225 The process of separating Ac, Methods that include...

[0177] 2. The process of preparing the phosphate-modified titania material is as follows: A step of mixing titania with a phosphate solution to produce a diluted titania solution, The steps include stirring the diluted titania solution, The process involves extracting phosphate-modified titania from the diluted titania solution by draining the phosphate solution, A step of washing the phosphate-modified titania so that washed phosphate-modified titania is produced, A step of drying the washed phosphate-modified titania so that dried phosphate-modified titania is produced, The method described in Clause 1, including the method described in Clause 1.

[0178] 3. The phosphate solution is the method according to clause 1 or 2, comprising H3PO4.

[0179] 4. The method according to any one of claims 1 to 3, wherein the phosphate solution comprises one of 1.0 M H3PO4, 0.1 to 0.5 M H3PO4, 1 to 5 M H3PO4, and 5 to 10 M H3PO4.

[0180] 5. The method according to any one of claims 1 to 4, wherein the step of stirring the diluted titania solution includes stirring the diluted titania solution at a speed in the range of 10 rpm to 2000 rpm.

[0181] 6. The method according to any one of claims 1 to 5, wherein the step of stirring the diluted titania solution includes stirring the diluted titania solution for a duration of 0.1 to 100 hours.

[0182] 7. The step of stirring the diluted titania solution includes the step of stirring the diluted titania solution at a temperature within the range of 10 to 100 °C, and the method according to any one of clauses 1 to 6.

[0183] 8. The step of extracting the phosphate-modified titania includes the step of allowing the diluted titania solution to settle, and the method according to any one of clauses 1 to 7.

[0184] 9. The step of extracting the phosphate-modified titania includes the step of allowing the diluted titania solution to settle for 1 hour, and the method according to any one of clauses 1 to 8.

[0185] 10. The step of washing the phosphate-modified titania includes the step of washing the phosphate-modified titania one or more times in deionized water, and the method according to any one of clauses 1 to 9.

[0186] 11. The step of washing the phosphate-modified titania includes the step of washing the phosphate-modified titania one or more times in 1 to 100 ml of deionized water, and the method according to any one of clauses 1 to 10.

[0187] 12. The step of drying the washed phosphate-modified titania includes the step of placing the washed residue on a heating device, and the method according to any one of clauses 1 to 11.

[0188] 13. The step of drying the washed phosphate-modified titania includes the step of placing the washed residue on a heating device at a temperature within the range of 50 to 150 °C, and the method according to any one of clauses 1 to 12.

[0189] 14. The method according to any one of the claims 1 to 13, wherein the step of drying the washed phosphate-modified titania includes placing the washed residue on a heating device at a temperature in the range of 50 to 150°C for 1 hour.

[0190] 15. The method according to any one of the claims 1 to 14, wherein the step of mixing titania includes mixing about 1.0 g of titania with about 125 ml of the solution.

[0191] 16. The solution is the method according to any one of the claims 1 to 15, having a pH in the range of 3.6 to 4.3.

[0192] 17. The method according to any one of claims 1 to 16, wherein the solution is the result of a Th purification process and comprises at least one of NaNO3, HOA, NaOA, or HNO3.

[0193] 18. The method according to any one of claims 1 to 17, wherein the step of contacting the solution includes the step of contacting the solution with the phosphate-modified titania material in a column containing the phosphate-modified titania material.

[0194] 19. The column flow rate is within the range of 2 to 10 mL / h, as described in any one of clauses 1 to 18.

[0195] 20. The titania material is a porous TiO2 material as described in any one of the claims 1 to 19.

[0196] twenty one. The method according to any one of the claims 1 to 20, wherein the elution rate of the washing solution is in the range of 30 to 60 mL / h.

[0197] twenty two. Before contacting the column, 229The method according to any one of the clauses 1 to 21, further comprising the step of discharging a residual solution containing Th.

[0198] twenty three. The step of discharging the residual solution is: A step of drying the residual solution so that a solid residue is produced, A step of eluting the solid residue using an elution solution so that an eluted residue is generated, 229 The process involves passing the recovery resin through the eluted residue so that Th is recovered, 229 The process of recovering Th, The method described in any one of the clauses 1 to 22, including the method described in any one of the clauses 1 to 22.

[0199] twenty four. The elution solution is the method described in any one of the clauses 1 to 23, comprising HNO3.

[0200] twenty five. The elution solution is the method described in any one of the clauses 1 to 24, comprising 0.01 to 10 M HNO3.

[0201] 26. The recovered resin is the method according to any one of the clauses 1 to 25, comprising UTEVA resin.

[0202] 27. 229 The process for recovering Th is performed at a rate of 99.253±0.004% or higher. 229 The method according to any one of clauses 1 to 26, including a step of recovering Th.

[0203] 28. The method according to any one of the claims 1 to 27, wherein the step of contacting the solution with the ion exchange material includes the step of contacting the solution with the ion exchange material in a column.

[0204] 29. The step of bringing the solution into contact with the ion exchange material is performed so that a Th-supported material is generated.229 The method according to any one of the claims 1 to 28, comprising the step of sorbing Th onto the titania material.

[0205] 30. The method according to any one of the claims 1 to 29, wherein the step of elution includes a step of using an eluent containing an HOA / NaOA solution.

[0206] 31. generated 225 The process of collecting Ac is In the concentrated elution mixture 228 From Ra 225 The process of separating Ac, Separation from the concentrated elution mixture 225 Inter or separated 228 A step of collecting at least one of Ra, The method described in any one of the clauses 1 to 30, including the method described in any one of the clauses 1 to 30.

[0207] 32. Separated 225 Inter or separated 228 The step of collecting at least one of the Ra is to separate 225 Inter or separated 228 The method described in any one of the clauses 1 to 31, comprising the step of collecting at least one of the Ras with a collection rate of more than 96%.

[0208] 33. The P-modified titania material has an average particle size in the range of 5 to 100 μm, as described in any one of the claims 1 to 32.

[0209] 34. A method for separating Ac from a Ra / Ac mixture, A step of concentrating the Ra / Ac mixture in a first solution, The process involves passing the first resin through the Ra / Ac mixture, The step of adding the second solution, The process involves passing a second resin through the aforementioned Ra / Ac mixture, A step to separate Ra from Ac so that separated Ra and separated Ac are produced, Methods that include...

[0210] 35. The first solution is the method according to clause 34, comprising HNO3.

[0211] 36. The first solution is the method according to clause 34 or 35, wherein the first solution contains HNO3 at a concentration in the range of 0.1 to 10 M.

[0212] 37. The method according to any one of the claims 34 to 36, wherein the first resin includes a UTEVA resin.

[0213] 38. The second solution is the method according to any one of the claims 34 to 37, comprising HNO3.

[0214] 39. The method according to any one of the claims 34 to 38, wherein the second solution contains HNO3 in a concentration in the range of 0.01 to 10 M.

[0215] 40. The method according to any one of the claims 34 to 39, wherein the second resin includes a rare earth resin.

[0216] 41. The method according to any one of the claims 34 to 40, further comprising the step of drying the separated Ra and the separated Ac so that dried Ra and a first dried Ac are produced.

[0217] 42. The method according to any one of claims 34 to 41, further comprising the step of diluting the dried Ra and the first dried Ac so that a diluted Ra and a first diluted Ac are produced, respectively.

[0218] 43. The method according to any one of claims 34 to 42, wherein the step of diluting the dried Ra includes the step of adding a third solution to the dried Ra.

[0219] 44. The third solution is the method according to any one of the clauses 34 to 43, comprising HNO3.

[0220] 45. The third solution is the method according to any one of the claims 34 to 44, comprising HNO3 at a concentration in the range of 0.1 to 10 M.

[0221] 46. The method according to any one of claims 34 to 45, wherein the step of diluting the first dried Ac includes adding a fourth solution to the first dried Ac so that a first diluted Ac is produced.

[0222] 47. The fourth solution is the method according to any one of the clauses 34 to 46, comprising HNO3.

[0223] 48. The method according to any one of the claims 34 to 47, wherein the fourth solution contains HNO3 in a concentration in the range of 0.01 to 10 M.

[0224] 49. A step of drying the first diluted Ac so that a second dried Ac is produced, A step of diluting the second dried Ac in a fifth solution so that a second diluted Ac is produced, The method described in any one of the clauses 34 to 48, further including the method described in any one of the clauses 34 to 48.

[0225] 50. The fifth solution is the method according to any one of the claims 34 to 49, comprising HNO3.

[0226] 51. The fifth solution is the method according to any one of the claims 34 to 50, comprising 6 M HNO3.

[0227] 52. A second step involves passing one or more third resins through the diluted Ac, The process involves collecting the aforementioned Ac and generating the collected Ac as the final product, The method described in any one of the clauses 34 to 51, further including the method described in any one of the clauses 34 to 51.

[0228] 53. The method according to any one of the claims 34 to 52, wherein the one or more of the aforementioned third resins include one or more UTEVA resins.

[0229] 54. The collected Ac is 225 The method described in any one of the clauses 34 to 53, including Ac.

[0230] 55. Ac generation generator, The first part of the generator, The column body defines the internal chamber, A first access port in the first part of the generator, which provides access to the internal chamber, The phosphate-modified titania material in the internal chamber, a certain amount 229 A phosphate-modified titania material supporting Th, A generator equipped with the following features.

[0231] 56. The second part of the generator, The second access port in the second part of the generator, Furthermore, The first portion of the generator is the top portion of the generator, The first access port is an upper valve, The second portion of the generator is the bottom portion of the generator, The generator according to Clause 55, wherein the second access port is a bottom valve or a U-tube.

[0232] 57. The internal chamber receives a certain amount of access through at least one of the first access port or the second access port. 229 A generator according to clause 55 or 56, comprising a filter for preventing the removal of the phosphate-modified titania material supporting Th.

[0233] 58. The generator according to any one of clauses 55 to 57, wherein the shape of the column body is one of capsule-shaped (spherical cylindrical), cylindrical, spherical, conical, pyramidal, frustoconical, or frustoconical.

[0234] 59. The generator according to any one of the clauses 55 to 58, wherein the first and second parts form a seal to the internal chamber.

[0235] 60. The generator according to any one of the clauses 55 to 59, wherein the first and second parts are removably attached to the column body.

[0236] 61. The generator according to any one of the clauses 55 to 60, wherein the first part, the column body, and the second part are integrally formed.

[0237] 62. A generator as described in any one of the clauses 55 to 61, further including a sealable third access port.

[0238] 63. A generator according to any one of the clauses 55 to 62, further comprising a diffuser within the second part described above.

[0239] 64. The diffuser comprises a perforated plate including holes, The generator according to any one of the clauses 55 to 63, wherein the perforation is sized to prevent the phosphate-modified titania material from passing through the perforation.

[0240] 65. The generator according to any one of the clauses 55 to 64, wherein the perforation is configured to allow a solvent to pass through the perforation.

[0241] 66. A system for separating Ra and Ac from a Ra / Ac mixture, A first separation column comprising a first separation column having a first resin and a second resin in separate parts of a first internal chamber of the first separation column, A second separation column comprising a second separation column having a plurality of second resins in separate parts of a second internal chamber of the second separation column, A system equipped with these features.

[0242] 67. The system according to Clause 66, wherein the first resin comprises a UTEVA resin.

[0243] 68. The system according to clause 66 or 67, wherein the second resin comprises a rare earth resin.

[0244] 69. The system according to any one of the clauses 66 to 68, wherein the first separation column comprises a sealable first access port configured to allow the addition and removal of the Ra / Ac mixture and the first resin.

[0245] 70. The system according to any one of clauses 66 to 69, wherein the second separation column comprises a sealable second access port configured to allow the addition and removal of dried Ra residue, dried Ac residue, or the second resin.

[0246] 71. Ac generation generator, The first part of the generator, The first fluid valve in the first portion of the generator, The column body defines the internal chamber, The phosphate-modified titania material in the internal chamber, a certain amount 229 A phosphate-modified titania material supporting Th, A first separation column comprising a first separation column having a first resin and a second resin in separate parts of a first internal chamber of the first separation column, A second separation column comprising a second separation column having a plurality of first resins in separate parts of a second internal chamber of the second separation column, A generator equipped with the following features.

[0247] 72. A method for preparing an Ac generation generator, A step of circulating a pretreatment solution at a predetermined circulation rate within a column containing titania material for a predetermined duration, After the circulating step, the process involves supplying the Th substance onto the titania material in the column at a predetermined supply rate so that a Th-supported titania material can be obtained. A step of washing the Th-supported titania material at a predetermined washing speed, Methods that include...

[0248] 73. The method according to Clause 72, wherein the pretreatment solution comprises at least one of acetic acid (HOA) or sodium acetate (NaOA).

[0249] 74. The method according to clause 72 or 73, wherein the pretreatment solution comprises at least one of 0.1 M HOA or 0.1 M NaOA.

[0250] 75. The method according to any one of the claims 72 to 74, wherein the pretreatment solution comprises at least one of 0.25 M HOA or 0.25 M NaOA.

[0251] 76. The method according to any one of the provisions 72 to 75, wherein the predetermined circulation rate is equal to either 60 ml / h or 300 ml / h.

[0252] 77. The acetic acid having a pKa of 4.2, according to the method according to any one of the claims 73 to 76.

[0253] 78. The method according to any one of the clauses 72 to 77, wherein the Th retention rate of the Th-supported titania material is in the range of 97.00 to 99.99%.

[0254] 79. The column comprises 5 g of TiO2, 51.6 g of TiO2, or one of 5 g to 1000 g of TiO2, as described in any one of clauses 72 to 78.

[0255] 80. The method according to any one of the clauses 72 to 79, wherein the pH of the pretreatment solution is within the range of 3.6 to 4.3.

[0256] 81. The method according to any one of the claims 72 to 80, wherein the supply rate of the Th substance is one of 2 ml / h and 10 ml / h.

[0257] 82. The method according to any one of the provisions 72 to 81, wherein the predetermined washing rate is one of 2 ml / h and 10 ml / h.

[0258] 83. The method according to any one of the provisions of 72 to 82, wherein the predetermined supply rate and the predetermined washing rate are equal.

[0259] 84. The method according to any one of claims 72 to 83, wherein the step of supplying the Th substance into the column includes the step of supplying 0.096 g of Th in 10 ml of the pretreatment solution.

[0260] 85. The method according to any one of claims 72 to 84, wherein the step of supplying the Th substance into the column includes the step of supplying either 0.092 g of Th in 20 ml of the pretreatment solution or 0.098 g of Th in 20 ml of the pretreatment solution.

[0261] 86. The method according to any one of claims 72 to 85, wherein the step of supplying the Th substance into the column includes the step of supplying 1.005 g of Th in 500 ml of the pretreatment solution.

[0262] 87. The method according to any one of the provisions 72 to 86, wherein the predetermined duration is approximately 6 hours.

[0263] 88. generated by any one of clauses 1 through 87 225 A pharmaceutical composition containing Ac.

[0264] 89. The pharmaceutical composition according to Clause 88, further comprising a pharmaceutically acceptable carrier.

[0265] 90. 225 Ac is bound to an antibody in the pharmaceutical composition described in Clauses 88-89.

[0266] 91. A method of treating a patient's cancer, A method comprising the step of administering a pharmaceutical composition described in any one of clauses 88 to 90 to the patient.

[0267] 92. The method according to Clause 91, wherein the cancer is breast cancer, leukemia, lymphoma, brain tumor, liver cancer, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, or bone cancer.

[0268] Unless otherwise specified, all numbers used in this specification and in the claims to represent quantities, molecular weights, and other properties of components, reaction conditions, etc., should be understood in all cases to be modified by the term "approximately." Therefore, unless otherwise specified, the numerical parameters described in the following specification and in the attached claims are approximations that may vary depending on the desired properties to be obtained.

[0269] While the numerical ranges and parameters representing the broad scope of this technology are approximations, the values ​​shown in the examples are reported as accurately as possible. However, any numerical value inherently contains a certain error that inevitably arises from the standard deviation found in each test measurement.

[0270] It will be apparent that the systems and methods described herein are well-adapted to achieve the objectives and benefits described, as well as the objectives and benefits inherent therein. Those skilled in the art will recognize that the methods and systems described herein can be implemented in many forms and are not limited to the exemplary examples and embodiments described above. In this regard, any number of configurations from the various embodiments described herein may be combined into a single embodiment, and alternative embodiments having fewer or more configurations than all of the configurations described herein are also conceivable.

[0271] While various embodiments have been described with respect to the purposes of this disclosure, various changes and modifications are possible, provided they fall well within the scope anticipated by this disclosure. Numerous other changes are also possible, which are readily apparent to those skilled in the art and are encompassed within the spirit of this disclosure.

[0272] This disclosure describes some embodiments of the Art with reference to the accompanying drawings, which show only some of the possible embodiments. However, other embodiments can be embodied (implemented) in a variety of many forms, and these other embodiments should not be construed as being limited to the embodiments described herein. Rather, these embodiments are provided so as to make this disclosure complete and comprehensive and to fully convey the scope of the possible embodiments to those skilled in the art.

[0273] Specific examples are described herein, but the scope of the Art is not limited to these specific examples. Those skilled in the art will recognize other examples or modifications that fall within the scope of the Art. Therefore, specific structures, actions (operations) or media are disclosed only as examples. Furthermore, examples of the Art may combine multiple elements or components that are generally disclosed but not expressly illustrated in combination, unless otherwise stated herein. The scope of the Art is defined by the following claims and their equivalents. [Brief explanation of the drawing]

[0274] [Figure 1] This is a schematic diagram of the decay chain from 233U to 229Th and its subsequent daughter nuclides. [Figure 2] This is a schematic diagram of the process flow for Ac production according to various embodiments of this disclosure. [Figure 3] This plot shows the decay chain of 232Th. [Figure 4] This plot shows the pH-dependent change in the distribution coefficient of Th4+ uptake by nanoporous TiO2 acceptance in various embodiments of this disclosure. [Figure 5] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 6] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 7]This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 8] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 9] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 10] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 11] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 12] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 13] This is a plot of the change in Th concentration with respect to elution amount in various embodiments of the present disclosure. [Figure 14] Multiple SEM images of surface-modified TiO2 materials according to various embodiments of this disclosure are shown. [Figure 15A] These are SEM images of TiO2 starting materials and synthesized materials using various principles of this disclosure. [Figure 15B] These are SEM images of TiO2 starting materials and synthesized materials using various principles of this disclosure. [Figure 15C] These are SEM images of TiO2 starting materials and synthesized materials using various principles of this disclosure. [Figure 15D] These are SEM images of TiO2 starting materials and synthesized materials using various principles of this disclosure. [Figure 16] This plot shows the pH-dependent changes in the distribution coefficient of Th4+ uptake by TiO2 and surface-modified TiO2 according to various embodiments of this disclosure. [Figure 17] This is a plot showing the radioactivity and recovery rates of 228Ra and 228Ac according to various embodiments of this disclosure. [Figure 18] This is a plot showing the radioactivity and recovery rates of 228Ra and 228Ac according to various embodiments of this disclosure. [Figure 19] This is a plot showing the radioactivity and recovery rates of 228Ra and 228Ac according to various embodiments of this disclosure. [Figure 20] This is a schematic diagram illustrating the elution behavior of 228Ra and 228Ac in response to Th supply, according to various embodiments of this disclosure. [Figure 21] This is an exemplary elution graph at Th saturation according to various embodiments of the present disclosure. [Figure 22] This is an exemplary elution graph at Th saturation according to various embodiments of the present disclosure. [Figure 23] This disclosure presents an example of a method to reduce Ra sorption onto IX material in a column and thereby increase the recovery rate of Ra, based on various embodiments of this disclosure. [Figure 24] An example of a generator in the form of a column packed with IX material is shown. [Figure 25] Another example of a generator in the form of a column packed with IX material is shown. [Figure 26] This flowchart shows a method for generating Ac according to various embodiments of the present disclosure. [Figure 27] This flowchart shows methods for preparing phosphate-modified titania materials according to various embodiments of this disclosure.

Claims

1. A method for generating Ac, A step of preparing a phosphate-modified titania material so that an ion exchange material is generated, To generate thorium-supported ion exchange material and contact solution, ２２９ A step of bringing a solution containing Th into contact with the ion exchange material, ２２５ A step of eluting the thorium-supported ion exchange material using a washing solution so that an Ac elution solution is generated, A step of concentrating the solution to be eluted so that a mixture to be eluted is produced, From other radioactive isotopes in the aforementioned eluted mixture ２２５ The process of separating Ac, Methods that include...

2. The process of preparing the phosphate-modified titania material is as follows: A step of mixing titania with a phosphate solution to produce a diluted titania solution, The steps include stirring the diluted titania solution, The process involves extracting phosphate-modified titania from the diluted titania solution by draining the phosphate solution, A step of washing the phosphate-modified titania so that washed phosphate-modified titania is produced, A step of drying the washed phosphate-modified titania so that dried phosphate-modified titania is produced, The method according to claim 1, including the method described in claim 1.

3. The phosphate solution is H ３ PO ４ The method according to claim 2, including the method described in claim 2.

4. The phosphate solution is 1.0 M H ３ PO ４ , 0.1 - 0.5 M H ３ PO ４ , 1 - 5 M H ３ PO ４ , and 5 - 10 M H ３ PO ４ The method according to claim 2, comprising one of them.

5. The method according to claim 2, wherein the step of stirring the diluted titania solution includes stirring the diluted titania solution at a speed within the range of 10 rpm to 2000 rpm.

6. The method according to claim 2, wherein the step of stirring the diluted titania solution includes stirring the diluted titania solution for a duration of 0.1 to 100 hours.

7. The method according to claim 2, wherein the step of stirring the diluted titania solution includes stirring the diluted titania solution at a temperature in the range of 10 to 100°C.

8. The method according to claim 2, wherein the step of extracting the phosphate-modified titania includes the step of clarifying the diluted titania solution.

9. The method according to claim 2, wherein the step of extracting the phosphate-modified titania includes the step of clarifying the diluted titania solution for one hour.

10. The method according to claim 2, wherein the step of washing the phosphate-modified titania includes washing the phosphate-modified titania once or multiple times in deionized water.

11. The method according to claim 2, wherein the step of washing the phosphate-modified titania includes washing the phosphate-modified titania once or multiple times in 1 to 100 ml of deionized water.

12. The method according to claim 2, wherein the step of drying the washed phosphate-modified titania includes the step of placing the washed residue on a heating device.

13. The method according to claim 2, wherein the step of drying the washed phosphate-modified titania includes the step of placing the washed residue on a heating device with a temperature in the range of 50 to 150°C.

14. The method according to claim 2, wherein the step of drying the washed phosphate-modified titania includes placing the washed residue on a heating device at a temperature in the range of 50 to 150°C for one hour.

15. The method according to claim 2, wherein the step of mixing titania includes mixing about 1.0 g of titania with about 125 ml of the phosphate solution.

16. ２２９ The method according to claim 1, wherein the solution containing Th has a pH in the range of 3.6 to 4.

3.

17. ２２９ The solution containing Th is the result of the Th purification process, and NaNO ３ , HOA, NaOA, or HNO ３ The method according to claim 1, comprising at least one of the following.

18. ２２９ The step of contacting the solution containing Th in the column containing the phosphate-modified titania material ２２９ The method according to claim 1, comprising the step of contacting the solution containing Th with the phosphate-modified titania material.

19. The method according to claim 18, wherein the column flow rate is in the range of 2 to 10 mL / h.

20. The phosphate-modified titania material is porous TiO ２ The method according to claim 1, including the method described in claim 1.

21. The method according to claim 1, wherein the dissolution rate of the washing solution is in the range of 30 to 60 mL / h.

22. Before contacting the column, ２２９ The method according to claim 18, further comprising the step of discharging a residual solution containing Th.

23. The step of discharging the residual solution is: A step of drying the residual solution so that a solid residue is produced, A step of eluting the solid residue using an elution solution so that a eluted residue is generated, ２２９ A step of passing the recovery resin through the eluted residue so that Th is recovered, ２２９ The process of recovering Th, The method according to claim 22, including the method described in claim 22.

24. The elution solution is HNO ３ The method according to claim 23, including the method described in claim 23.

25. The elution solution is 0.01 to 10 M HNO ３ The method according to claim 23, including the method described in claim 23.

26. The method according to claim 23, wherein the recovered resin includes UTEVA resin.

27. ２２９ The process of recovering Th is performed at a rate of 99.253 ± 0.004% or higher. ２２９ The method according to claim 23, comprising the step of recovering Th.

28. ２２９ The step of bringing the solution containing Th into contact with the ion exchange material in a column ２２９ The method according to claim 1, comprising the step of bringing the solution containing Th into contact with the ion exchange material.

29. ２２９ The step of bringing the solution containing Th into contact with the ion exchange material is performed so that a Th-supported material is generated. ２２９ The method according to claim 1, comprising the step of sorbing Th onto the phosphate-modified titania material.

30. The method according to claim 1, wherein the step of eluting the thorium-supported ion exchange material using the washing solution includes a step of using an eluent containing an HOA / NaOA solution.

31. generated ２２５ The process further includes collecting Ac, The generated ２２５ The process of collecting Ac is, In the concentrated eluted mixture ２２８ From Ra ２２５ The process of separating Ac, Separation from the concentrated eluted mixture ２２５ Ac or separated ２２８ A step of collecting at least one of Ra, The method according to claim 1, including the method described in claim 1.

32. Separation from the concentrated eluted mixture ２２５ Ac or separated ２２８ The step of collecting at least one of the Ra is to separate the ２２５ Ac or the separated ２２８ The method according to claim 31, further comprising the step of collecting at least one of Ra with a collection rate of more than 96%.

33. The method according to claim 1, wherein the phosphate-modified titania material has an average particle size in the range of 5 to 100 μm.

34. A generator that generates Ac, The first part of the generator, The column body defines the internal chamber, A first access port in the first part of the generator, which provides access to the internal chamber, The phosphate-modified titania material in the internal chamber, a certain amount ２２９ A phosphate-modified titania material supporting Th, A generator equipped with the following features.

35. The second part of the generator, The second access port in the second part of the generator, Furthermore, The first portion of the generator is the top portion of the generator, The first access port is an upper valve, The second portion of the generator is the bottom portion of the generator, The generator according to claim 34, wherein the second access port is a bottom valve or a U-tube.

36. The internal chamber receives a certain amount of access through at least one of the first access port or the second access port. ２２９ The generator according to claim 35, comprising a filter for preventing the removal of the phosphate-modified titania material supporting Th.

37. The generator according to claim 34, wherein the shape of the column body is one of capsule-shaped (spherical cylindrical), cylindrical, spherical, conical, pyramidal, frustoconical, or frustoconical.

38. The generator according to claim 35, wherein the first and second portions form a seal to the internal chamber.

39. The generator according to claim 35, wherein the first and second parts are detachably attached to the column body.

40. The generator according to claim 35, wherein the first part, the column body, and the second part are integrally formed.

41. The generator according to claim 35, further comprising a sealable third access port.

42. The generator according to claim 35, further comprising a diffuser within the second portion.

43. The diffuser comprises a perforated plate including holes, The generator according to claim 42, wherein the perforation is sized to prevent the phosphate-modified titania material from passing through the perforation.

44. The generator according to claim 43, wherein the perforation is configured to allow a solvent to pass through the perforation.

45. A generator that generates Ac, The first part of the generator, The first fluid valve in the first part of the generator, The column body defines the internal chamber, The phosphate-modified titania material in the internal chamber, a certain amount ２２９ A phosphate-modified titania material supporting Th, A first separation column comprising a first separation column having a first resin and a second resin in separate parts of a first internal chamber of the first separation column, A second separation column comprising a second separation column having a plurality of first resins in separate parts of the second internal chamber of the second separation column, A generator equipped with the following features.

46. A method for preparing a generator that generates Ac, A step of circulating a pretreatment solution at a predetermined circulation rate within a column containing titania material for a predetermined duration, After the step of circulating the pretreatment solution, the step of supplying the Th substance onto the titania material in the column at a predetermined supply rate so that a Th-supported titania material is obtained, A step of washing the Th-supported titania material at a predetermined washing speed, Methods that include...

47. The method according to claim 46, wherein the pretreatment solution comprises at least one of acetic acid (HOA) or sodium acetate (NaOA).

48. The method according to claim 46, wherein the pretreatment solution comprises at least one of 0.1 M HOA or 0.1 M NaOA.

49. The method according to claim 46, wherein the pretreatment solution comprises at least one of 0.25 M HOA or 0.25 M NaOA.

50. The method according to claim 46, wherein the predetermined circulation rate is equal to one of 60 ml / h or 300 ml / h.

51. The method according to claim 47, wherein the acetic acid has a pKa of 4.

2.

52. The method according to claim 46, wherein the Th retention rate of the Th-supported titania material is in the range of 97.00 to 99.99%.

53. The column contains 5 g of TiO ２ 51.6g TiO ２ , or 5g to 1000g of TiO ２ The method according to claim 46, comprising one of the following.

54. The method according to claim 46, wherein the pH of the pretreatment solution is in the range of 3.6 to 4.

3.

55. The method according to claim 46, wherein the supply rate of the Th substance is one of 2 ml / h and 10 ml / h.

56. The method according to claim 46, wherein the predetermined washing rate is one of 2 ml / h and 10 ml / h.

57. The method according to claim 46, wherein the predetermined supply speed and the predetermined washing speed are equal.

58. The method according to claim 46, wherein the step of supplying the Th substance into the column includes the step of supplying 0.096 g of Th in 10 ml of the pretreatment solution.

59. The method according to claim 46, wherein the step of supplying the Th substance into the column includes the step of supplying one of 0.092 g of Th in 20 ml of the pretreatment solution and 0.098 g of Th in 20 ml of the pretreatment solution.

60. The method according to claim 46, wherein the step of supplying the Th substance into the column includes the step of supplying 1.005 g of Th in 500 ml of the pretreatment solution.

61. The method according to claim 46, wherein the predetermined duration is approximately 6 hours.

62. generated by the method according to any one of claims 1 to 33 or the method according to any one of claims 46 to 61 ２２５ A method for producing a pharmaceutical composition containing Ac.

63. A method for producing the pharmaceutical composition according to claim 62, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

64. ２２５ A method for producing the pharmaceutical composition according to claim 62, wherein Ac is bound to the antibody.

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