Separation and purification method for 64Cu in accelerator irradiation target

Abstract

The invention discloses a method for separating and purifying 64Cu in an accelerator irradiation target, which adopts a combined process of an anion column and an extraction resin column to obtain high-concentration and high-purity 64Cu which can be directly used for biomarkers and recover 64Ni at the same time under the condition of not using an organic solvent. The acidity of Cu component effluent in the anion column is similar to that of a column on a Cu resin column, and TK201 resin can be selected to convert the acidity of the Cu component effluent in the Cu resin column and further remove residual Ni in the Cu component effluent in order to solve the problem that the acidity of the Cu component effluent in the Cu resin column is too high. And triple resin columns are superposed, so that a 64Cu final product with higher purity and more appropriate acidity can be obtained.

Description

Technical Field

[0001] This invention belongs to the field of medical radioisotope separation and purification technology, and specifically relates to a method for separating and purifying radioisotopes in accelerator irradiation targets. 64 Methods for the separation and purification of Cu. Background Art

[0002] Over the past two decades, the widespread use of medical cyclotrons has spurred a significant increase in the medical applications of radioisotopes. Simultaneously, the extensive use of positron emission tomography (PET) in oncology and the rapid global adoption of PET-CT cameras have revolutionized nuclear medicine. Researchers have explored and reported on various medical radioisotopes; however, due to their nuclear properties (half-life, type of radiation, energy, etc.), many positron-emitting and long-lived radionuclides are not suitable for widespread use in nuclear medicine. Suitable half-lives, low positron energies, and low gamma radiation abundance are crucial. 64 Cu (T1 / 2 = 12.7 h) is one of the two “emerging PET nuclides” recommended by the International Atomic Energy Agency.

[0003] 64 Cu nuclides are typically obtained in two ways: (1) using a reactor, mainly through... 63 Cu(n, γ) 64 Cu and 64 Zn(p, n) 64 (2) Obtained by Cu reaction; using an accelerator, mainly with nickel as the target material. 64 Ni(p, n) 64 Cu or 64 Ni(d, 2n) 64 Obtained by Cu reaction, or by using zinc as a target material 68 Zn(p, αn) 64 Cu is obtained through reaction. Currently, for 64 Separation and purification of Cu, such as Figure 1 As shown, anion exchange resins AG1×4 or AG1×8 are often used: a higher concentration of hydrochloric acid is used to... 64 After dissolving the Ni target and adjusting the acidity, it is directly injected into an activated anion exchange column. Impurity ions and the target element are separated and recovered using washing and elution solutions, respectively. The target element Ni typically elutes with the column. The washing solution is usually a high-concentration hydrochloric acid solution, such as 6-7M hydrochloric acid, or a solution with reduced hydrochloric acid concentration and the addition of an organic solvent, such as 3M hydrochloric acid solution with 10% ethanol. Deionized water can be used directly as the elution solution. This process is simple. 64 Cu products have low acidity and can be directly used for subsequent applications such as biolabeling. However, during the elution process, small amounts of impurity ions such as Co, Ga, Au, and Tl may also be present.64 Cu effluent is the primary factor affecting its purity. Besides this, some separation processes use AG50W×8 cation exchange resin, or a combination of Cu extraction resin and TBP and TK201 resin. In cation exchange column processes, the washing buffer is a low-concentration hydrochloric acid solution containing organic solvents, such as a 0.5M hydrochloric acid:acetone = 2:8 mixture; the eluent is a 2M hydrochloric acid:acetone = 1:9 mixture. Because cation exchange column separation processes require the use of volatile organic solvents such as acetone, the experimental risks increase; furthermore, the Cu component in the eluent needs to be evaporated, reconstituted, and acidified to obtain the final product, making the process quite cumbersome. Cu resin separation processes, limited by their resin extraction performance, can only operate at pH > 2, which is incompatible with strongly acidic target solutions. Therefore, sodium hydroxide is often added to adjust the acidity of the target solution, thereby introducing more impurity ions, such as Na+. + This not only increases the difficulty of recovering Ni or Zn from the target element, but also increases... 64 The difficulty of purifying Cu. Summary of the Invention

[0004] In view of the above-mentioned shortcomings of the existing technology, the purpose of this invention is to provide a method for separating and purifying 64Cu without using organic solvents for existing accelerator irradiated Ni target solutions, thereby recovering the target element 64Ni while improving its ability to remove impurity ions. To achieve the above objective, this invention provides the following technical solution: On the one hand, this invention proposes a method for separating and purifying 64Cu in an accelerator irradiation target, comprising the following steps: (1) Target dissolution: In the embodiments provided by the present invention, after the target is cut, it is immersed in a mixed solution of hydrochloric acid with a concentration of c1 and a volume of V1 and concentrated nitric acid with a volume of V2, and heated until the target is completely dissolved.

[0005] Furthermore, c1 is 7-9M, preferably 8M, and the target mass: V1:V2 = 1:90-110:9-11, with a preferred ratio of 1:100:10. The target mass unit is g, and the volume unit is mL.

[0006] (2) Target element recovery: Column packing: The anion exchange resin is soaked in hydrochloric acid solution for more than 30 minutes and then packed into the separation column to form an anion column; the anion exchange resin is selected from AG1×8 anion exchange resin or AG1×4 anion exchange resin.

[0007] Pre-equilibration of resin acidity: First, rinse the column with 10-20 mL of deionized water, then rinse the column with hydrochloric acid of concentration C2 to balance the acidity in the anion exchange resin column to be consistent with C2. Column separation: The target dissolution solution obtained in step (1) is pumped onto the anion exchange column at a certain flow rate, and then hydrochloric acid with a volume of V3 and a concentration of c2 is added. The two effluents are combined to obtain effluent I, which can provide a target for electroplating reprocessing. 64 Ni mother liquor; add hydrochloric acid solution with concentration c3 and volume V4 to the column, and collect effluent II for the next step. 64 Cu purification.

[0008] Furthermore, c2 is 8.5-9.5M, preferably 9M; c3 is 0.001-0.01M, pH=2-3, preferably 0.01M, pH=2; V3 is 30-35mL, preferably 35mL; V4 is 25-35mL, preferably 30mL; the total flow rate is 1mL / min.

[0009] Target mass: anion exchange resin mass = 1:5-7, preferably 1:6.

[0010] (3) 64 Cu purification: Column packing: Soak Cu resin (Triskem, 100-150μm, 0.3g) in hydrochloric acid solution for more than 30 minutes, and then pack it into the separation column to form a Cu resin column; Pre-equilibration of resin acidity: First, rinse the column with 10-20 mL of deionized water, then rinse the column with hydrochloric acid of concentration C3 to balance the acidity in the Cu resin column to be consistent with C3. Column separation: The product obtained in step (2) 64 The Cu eluent was loaded onto the Cu resin column at a certain flow rate, and then hydrochloric acid with a volume of V5 and a concentration of c3 was added at a flow rate of 1 to obtain effluent III. Next, hydrochloric acid solution with a volume of V6 and a concentration of c1 was pumped in at a flow rate of 2, and effluent IV was collected for the next step. 64 Acidity adjustment of Cu products.

[0011] Furthermore, V5 is 10-15 mL, preferably 10 mL; V6 is 1.5-3 mL, preferably 2 mL. Flow rate 1 is 1 mL / min, and flow rate 2 is 6 mL / min.

[0012] (4) 64 Acidity adjustment of Cu products: Column packing: Soak TK201 resin (Triskem, 100-150μm, 0.7g) in hydrochloric acid solution for more than 30 minutes, and then pack it into the separation column to form a TK201 resin column; Pre-equilibration of resin acidity: First, rinse the column with 10-20 mL of deionized water, then rinse the column with 10 mL of hydrochloric acid with concentration c1 to equilibrate the acidity in the TK201 resin column to be consistent with c1. Column separation: The effluent IV obtained in step (3) is loaded onto a TK201 resin column, and then a 5M NaCl solution with a volume of V5 is pumped in to obtain effluent V. Then, a volume of air with a volume of V5 is pumped in, and finally, a hydrochloric acid solution with a concentration of c3 with a volume of V7 is added and effluent VI is collected to obtain a final product that can be directly biolabeled.

[0013] Furthermore, the flow rate is 1 mL / min throughout the process; V7 is 4.5-5.5 mL, preferably 5 mL.

[0014] Preferably, the target contains Co, Ga, Cu, and Ni elements, which are removed as impurities by the method provided by the present invention.

[0015] Secondly, the present invention also provides a product obtained by using the separation and purification method provided by the present invention, the acidity range of which is pH=2-3.

[0016] Before purifying Cu with Cu resin, this invention first performs anion exchange column separation. Since the target solution is typically a high-acid environment of 7-9M hydrochloric acid, this operation avoids acid adjustment, allowing the product separated by the anion exchange column to be directly used for Cu resin purification. Simultaneously, the double purification of Cu with anion exchange resin enhances the process's ability to remove impurities. After Cu resin purification, this invention uses a TK201 resin column for acidity adjustment. This yields a final product with suitable acidity, which can be directly used for biolabeling. Compared to conventional methods that involve large-volume processes such as organic solvent evaporation and concentration before acidity adjustment, this method is more cost-effective. Furthermore, the TK201 resin column further purifies the product, improving the removal of Ni impurities. Compared to existing technologies, the beneficial effects of this invention are: 1. This invention provides a solution for dissolving irradiated nickel targets. 64 The separation and purification process for Cu employs a combined anion exchange column and extraction resin column technique, yielding high-concentration, high-purity Cu that can be directly used for biolabeling without the use of organic solvents. 64 Cu, and can be recovered simultaneously 64 Ni.

[0017] 2. In this invention, the acidity of the Cu component effluent from the anion exchange column is similar to that of the Cu resin column. To address the issue of excessively high acidity in the Cu component effluent from the Cu resin column, TK201 resin can be used to convert its acidity, and it can also further remove residual Ni. The triple resin column stacking yields a product with higher purity and more suitable acidity. 64 Cu final product.

[0018] 3. This invention, through research, has found that the acidity of the hydrochloric acid solution significantly affects the purification and separation effect of Cu in each step. Different acidities affect the resin's effect on Cu. 2+The adsorption capacity of Cu affects the recovery rate. The acidity range disclosed in this invention is suitable for the purification and separation of Cu and has a high recovery rate. Attached Figure Description

[0019] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0020] Figure 1 This is a process flow diagram of anion exchange resin column separation, which is commonly used today. Figure 2 This is a process flow diagram of the anion exchange resin-extraction resin combined separation process used in this embodiment. Detailed Implementation

[0021] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0022] In this embodiment, the decontamination coefficient is calculated using the following formula: Df=N0 / NA, Where Df is the decontamination coefficient, N0 is the content of the element in the target solution before separation, and NA is the content of the element in the product after separation.

[0023] Example 1 like Figure 2 As shown, the specific steps include the following: (1) Target dissolution. Take 200 μL of Co (100 ppm), 200 μL of Ga (100 ppm), and 200 μL of Cu (100 ppm) into a 100 mL beaker, add 1.36 g of Ni(NO3)2•6H2O, and then add 40 mL of 8M hydrochloric acid and 5 mL of concentrated nitric acid. Dissolve by sonication to obtain the target simulation solution.

[0024] (2) Target element recovery. Column packing: Soak AG1×8 anion exchange resin (Bio-rad, 100-200 mesh) in 0.1M hydrochloric acid solution for more than 30 minutes, and then pack it into the separation column to form an anion exchange column. Resin acidity pre-equilibration: First, wash the column with 10-20 mL of deionized water, and then wash it with 10 mL of 9M hydrochloric acid to balance the acidity in the anion exchange resin column to 9M. Column separation: Pump the target dissolution solution obtained in step (1) onto the anion exchange column at a flow rate of 1 mL / min, and then add 33 mL of 9M hydrochloric acid (eluent I). Combine and collect the two effluents (effluent I) for use. 64 Ni recovery can provide for the remanufacturing of electroplating targets.64 Ni mother liquor; add 30 mL of 0.01 M hydrochloric acid (eluent II) to the column, and collect effluent II for the next step. 64 Cu purification.

[0025] (3) 64 Cu purification. Column packing: Soak Cu resin (Triskem, 100-150μm, 0.3g) in 0.1M hydrochloric acid solution for at least 30 minutes, then pack it into the separation column to form a Cu resin column. Resin acidity pre-equilibration: First, wash the column with 10-20mL of deionized water, then wash it with 10mL of pH=2 hydrochloric acid to equilibrate the acidity of the Cu resin column to pH=2. Column separation: The Cu resin obtained in step (2) is... 64 Cu eluent was added to the Cu resin column at a flow rate of 1 mL / min, followed by 10 mL of hydrochloric acid solution at pH 2 (eluent III) to obtain effluent III; then 2 mL of 8M hydrochloric acid (eluent IV) was pumped in at a flow rate of 6 mL / min, and the effluent was collected for the next step. 64 Acidity adjustment of Cu products (effluent IV).

[0026] (4) 64 Acidity adjustment of Cu products. Column packing: Soak TK201 resin (Triskem, 100-150μm, 0.7g) in 8M hydrochloric acid solution for more than 30 minutes, and then pack it into the separation column to form a TK201 resin column. Resin acidity pre-equilibration: First, wash the column with 10-20mL of deionized water, and then wash it with 10mL of 8M hydrochloric acid to balance the acidity of the TK201 resin column to 8M. Column separation: The product obtained in step (3) 64 The Cu product solution was loaded onto a TK201 resin column at a rate of 1 mL / min; then 10 mL of 5 M NaCl solution (eluent V) was pumped in to obtain effluent V, followed by the pumping of 10 mL of air to remove residual liquid in the column, reducing dead volume and ensuring the next step; finally, 5 mL of 0.01 M hydrochloric acid (eluent VI) was added and effluent VI was collected. 64 Cu final product).

[0027] (5) The final Cu recovery rate was 93.1%, the solution acidity was about 0.01M (pH2), and the decontamination coefficient of Ni was greater than 50000, the decontamination coefficient of Co was greater than 50000, and the decontamination coefficient of Ga was greater than 10000.

[0028] Comparative Example 1: Anion exchange resin column separation process (1) Target dissolution. Take 200 μL of Co (100 ppm), 200 μL of Ga (100 ppm), and 200 μL of Cu (100 ppm) into a 100 mL beaker, add 1.36 g of Ni(NO3)2•6H2O, and then add 40 mL of 9M hydrochloric acid to dissolve by sonication to obtain the target simulation solution.

[0029] (2) Anion exchange column separation. 2g of AG1×4 anion exchange resin (Bio-rad, 100-200 mesh) was loaded into the separation column, and then eluted with 10mL of deionized water and 10mL of 9M hydrochloric acid at a flow rate of 1mL / min. The target simulation solution obtained in (1) was loaded onto the column, and then the anion exchange column was eluted with 5mL of 9M hydrochloric acid, 5mL of a mixture of 10% ethanol and 3M hydrochloric acid, and 5mL of deionized water in sequence.

[0030] (3) The final Cu recovery rate was 95.1%, the solution contained 3M hydrochloric acid and 10% ethanol; the decontamination coefficient of Ni was greater than 10000, the decontamination coefficient of Co was greater than 2000, and the decontamination coefficient of Ga was greater than 100.

[0031] Compared with Comparative Example 1, Example 1 involves more steps, resulting in a corresponding loss of Cu. The final Cu solution in Example 1 using the method of the present invention has an acidity of approximately 0.01 M (pH 2), which is suitable for direct use in biolabeling. Furthermore, the decontamination coefficients of Co, Ga, and Ni are much higher than those in Comparative Example 1, indicating that the resulting product has higher purity.

[0032] Comparative Example 2: Effect of Cu Resin Acidity Change on Column Loading (1) Target dissolution. Take 200 μL of Co (100 ppm), 200 μL of Ga (100 ppm), and 200 μL of Cu (100 ppm) into a 100 mL beaker, add 1.36 g of Ni(NO3)2•6H2O, and then add 40 mL of 8M hydrochloric acid and 5 mL of concentrated nitric acid. Dissolve by sonication to obtain the target simulation solution.

[0033] (2) Target element recovery. Column packing: Soak AG1×8 anion exchange resin (Bio-rad, 100-200 mesh) in 0.1M hydrochloric acid solution for more than 30 minutes, and then pack it into the separation column to form an anion exchange column. Resin acidity pre-equilibration: First, wash the column with 10-20 mL of deionized water, and then wash it with 10 mL of 9M hydrochloric acid to balance the acidity of the anion exchange resin column to 9M. Column separation: Pump the target dissolution solution obtained in step (1) onto the anion exchange column at a flow rate of 1 mL / min, and then add 30 mL of 9M hydrochloric acid. Combine and collect the two effluents; then add 30 mL of 1M hydrochloric acid to the column and collect the effluent for the next step. 64Cu purification.

[0034] (3) 64 Cu purification. Column packing: Soak Cu resin (Triskem, 100-150μm, 0.3g) in 0.1M hydrochloric acid solution for at least 30 minutes, then pack it into the separation column to form a Cu resin column. Resin acidity pre-equilibration: First, wash the column with 10-20mL of deionized water, then wash it with 10mL of 1M hydrochloric acid to equilibrate the acidity of the Cu resin column to 1M. Column separation: The Cu resin obtained in step (2) is... 64 Cu eluent was loaded into the Cu resin column at a flow rate of 1 mL / min, followed by 10 mL of 1 M hydrochloric acid solution; then 2 mL of 8 M hydrochloric acid was pumped in at a flow rate of 6 mL / min, and the eluent was collected for the next step. 64 Acidity adjustment of Cu products.

[0035] (4) 64 Acidity adjustment of Cu products. Column packing: Soak TK201 resin (Triskem, 100-150μm, 0.7g) in 8M hydrochloric acid solution for more than 30 minutes, and then pack it into the separation column to form a TK201 resin column. Resin acidity pre-equilibration: First, wash the column with 10-20mL of deionized water, and then wash it with 10mL of 8M hydrochloric acid to balance the acidity of the TK201 resin column to 8M. Column separation: The product obtained in step (3) 64 Cu product solution was loaded onto a TK201 resin column at a rate of 1 mL / min; then 10 mL of 5 M NaCl solution was pumped in, followed by 10 mL of air to remove residual liquid in the column, reducing dead volume while ensuring the next step; finally, 5 mL of 0.01 M hydrochloric acid was added and the effluent was collected.

[0036] (5) The final Cu recovery rate was 54.5%, the solution acidity was about 0.01M (pH2), and the decontamination coefficient of Ni was greater than 50000, the decontamination coefficient of Co was greater than 50000, and the decontamination coefficient of Ga was greater than 10000.

[0037] In Comparative Example 2, the acidity of the Cu resin used for column loading was 1M hydrochloric acid. At this point, the resin's effect on Cu... 2+ The adsorption capacity of Cu is relatively weak. 2+ As other impurity ions flow out, less of it flows out with the Cu eluent after loading onto the column, resulting in a lower recovery rate than in Example 1.

[0038] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A method for separating and purifying 64Cu in an accelerator irradiation target, characterized in that: The steps include: (1) Target dissolution: After the target is cut, it is dissolved in a mixed solution of hydrochloric acid and concentrated nitric acid; (2) Target element recovery: Anion exchange column is used to recover the target element Ni; (3) 64 Cu purification: Purification by Cu resin column; (4) 64 Cu product acidity adjustment: Use TK201 resin for separation.

2. The separation and purification method according to claim 1, characterized in that Step (1) includes the following processing: After the target is cut, it is immersed in a mixed solution of hydrochloric acid with a concentration of c1 and a volume of V1 and concentrated nitric acid with a volume of V2, and heated until the target is completely dissolved; Among them, c1 is 7-9M, target mass: V1:V2=1:90-110:9-11, target mass unit is g, volume unit is mL.

3. The separation and purification method according to claim 2, characterized in that Step (2) includes the following processing: Column loading: Soak the anion exchange resin in hydrochloric acid solution for more than 30 minutes, and then load it into the separation column to form an anion column; Resin acidity pre-balance: First, wash the column with 10-20 mL of deionized water, then wash the column with hydrochloric acid of concentration c2 to balance the acidity in the anion resin column to the same as c2; Column separation: The target solution obtained in step (1) is pumped onto the anion column at a certain flow rate, and then hydrochloric acid with a volume of V3 and a concentration of C2 is added. The two effluents are combined to provide a target for electroplating. 64 Ni mother liquor; add hydrochloric acid solution with a concentration of c3 and a volume of V4 to the column, and collect the effluent for the next step 64 Cu purification; Among them, c2 is 8.5-9.5M; c3 is 0.001-0.01M, pH=2-3; V3 is 30-35mL; V4 is 25-35mL.

4. The separation and purification method according to claim 3, characterized in that: In step (2), c2 is 9 M; c3 is 0.01 M, pH=2; V3 is 35 mL; V4 is 30 mL; and the total flow rate is 1 mL / min.

5. The separation and purification method according to claim 1, characterized in that: In step (2), the target mass: anion resin mass = 1:5-7.

6. The separation and purification method according to claim 1, characterized in that: Step (3) includes the following processing: Column loading: Soak the Cu resin in hydrochloric acid solution for more than 30 minutes, and then load it into the separation column to form a Cu resin column; Resin acidity pre-balance: First, wash the column with 10-20 mL of deionized water, then wash the column with hydrochloric acid of concentration c3, and balance the acidity in the Cu resin column to the same as c3; Column separation: The 64 The Cu eluent is loaded onto the Cu resin column at a certain flow rate, and then hydrochloric acid with a volume of V5 and a concentration of c3 is added at a flow rate of 1; then a hydrochloric acid solution with a volume of V6 and a concentration of c1 is pumped in at a flow rate of 2, and the effluent is collected for the next step 64 Cu product acidity adjustment; Among them, V5 is 10-15mL; V6 is 1.5-3mL.

7. The separation and purification method according to claim 6, characterized in that: In step (3), V5 is 10 mL; V6 is 2 mL.

8. The separation and purification method according to claim 3, characterized in that: Step (4) includes the following processing: Column loading: Soak TK201 resin in hydrochloric acid solution for more than 30 minutes, and then load it into the separation column to form a TK201 resin column; Resin acidity pre-balance: First, wash the column with 10-20 mL of deionized water, then wash the column with 10 mL of hydrochloric acid with a concentration of c1, and balance the acidity in the TK201 resin column to the same as c1; Column separation: The obtained 64 The Cu product solution is loaded onto the TK201 resin column, and then a 5M NaCl solution with a volume of V5 is pumped in, and then air with a volume of V5 is pumped in, and finally a hydrochloric acid solution with a volume of V7 and a concentration of c3 is added and the effluent is collected to obtain the final product that can be directly biolabeled; Among them, V7 is 4.5-5.5mL.

9. The separation and purification method according to claim 8, characterized in that: In step (4), the flow rate throughout the process was 1 mL / min; V7 was 5 mL.

10. A product obtained by the separation and purification method according to any one of claims 1 to 9.

Images