Cu-61 separation and purification method based on multi-stage resin combination

Abstract

A Cu-61 separation and purification method based on multistage resin combination comprises the following steps: step 1, placing an irradiated target material in HCl, heating until the target material is completely dissolved, and then filtering to obtain a clear solution; 2, filling a chromatographic column with ZR resin for activation; loading the clarified solution obtained in the step 1 to adsorb Ga ions in the clarified solution, and collecting effluent; washing the chromatographic column; step 3, filling AG1-X8 resin into a chromatographic column, loading the ZR resin effluent obtained in the step 2, and then washing; then carrying out gradient elution, and collecting an eluent; and 4, neutralizing the eluent obtained in the step 3, and evaporating and concentrating to a target volume. According to the method, a resin function cooperation mechanism is adopted, the ZR resin has super-strong selectivity and large adsorption capacity on Ga ions on the basis of a hydroxamic acid group, the AG1-X8 resin captures Cu ions through anion exchange, and Cu and Zn isotopes are accurately separated in combination with gradient elution.

Description

Technical Field

[0001] The present invention relates to the technical field of isotope separation and purification, and in particular to a Cu-61 separation and purification method based on multi-stage resin combination. Background Art

[0002] Copper-61( 61 Cu is a positron-emitting (β + ) radionuclide, which is widely used in positron emission tomography (PET) imaging and targeted radiotherapy. Its mainstream production method is to irradiate natural zinc target with protons, and then generate natZn(p,n) through the nuclear reaction 61 However, in addition to the 61 In addition to Cu, it usually contains a large amount of unreacted 64 Zn, by-products 68 Ga / 67 Ga and other metal impurities need to be separated through efficient separation process to obtain medical grade 61 Cu.

[0003] at present, 61 The purification technology of Cu mainly includes the following methods:

[0004] Single resin separation method: for example, using anion exchange resin (such as AG1-X8) to adsorb in high concentration hydrochloric acid (HCl) 61 Chloro complex of Cu Gradient elution is used to separate Zn and Ga. However, this method has limited efficiency in removing Ga (residue > 1 ppm) and requires a complex elution procedure.

[0005] Solvent extraction: selective extraction using chelating agents such as dithizone 61 Cu, but there are problems such as high toxicity of organic solvents, cumbersome operation steps, and long time consumption, which makes it difficult to adapt 61 Short half-life requirement of Cu.

[0006] Cation exchange method: adsorption by resins such as Dowex 50W under low acidity conditions 61 Cu 2+ , but cannot effectively separate Zn with similar charge density 2+ and Ga 3+ , resulting in insufficient purity.

[0007] The above methods have the following defects: Insufficient Ga removal efficiency: Ga 3+ In high concentrations of HCl, a stable With CuCl3 - The adsorption characteristics of the two are similar, and traditional anion resins are difficult to separate completely. 61 Cuzhong 68Ga residue (>0.5%) affects the safety of the developer.

[0008] Complex operation process: the existing method requires multiple switching of acidity or solvent system (such as HCl→HNO3→H2O), which prolongs the purification time and causes 61 Cu radioactivity loss (decay loss>30%).

[0009] Zn residual problem: Zn 2+ At low acidity, it is easy to react with Cu 2+ Co-adsorption and insufficient selectivity of the cation exchange resin result in residual Zn (>10 ppm) in the final product, interfering with the radiolabeling reaction.

[0010] Cost and scalability limitations: Relying on imported special resins (such as TK200) or high-purity chelating agents, the cost of industrial production is high and it is difficult to adapt to different forms of targets (liquid / solid zinc targets). Summary of the Invention

[0011] In order to overcome the defects of the prior art, the present invention discloses a Cu-61 separation and purification method based on multi-stage resin combination.

[0012] The Cu-61 separation and purification method based on multi-stage resin combination of the present invention comprises the following steps:

[0013] Step 1. Target dissolution and pretreatment

[0014] After irradiation 64 The Zn target was placed in HCl and heated until completely dissolved, and then the undissolved particles were removed by filtration to obtain 61 Cu 2+ 、Zn 2+ 、Ga 3+ clear solution of ions;

[0015] Step 2: ZR resin removes Ga impurities

[0016] The ZR resin was filled into the chromatographic column and activated with 6-12M HCl; the clear solution obtained in step 1 was loaded so that the Ga 3+ The ions are adsorbed and the effluent is collected. The effluent contains Cu 2+ 、Zn 2+ ion;

[0017] Flush the column to ensure Complete adsorption; M represents the concentration in moles per liter;

[0018] Step 3: Fill the AG1-X8 resin into the chromatographic column and equilibrate with 5 to 10 M HCl; load the ZR resin effluent obtained in step 2 into the AG1-X8 column, then rinse and equilibrate the column volume;

[0019] Then, Cu was gradient eluted with HCl at a concentration of 3 to 5 M, and the eluate containing 61Cu was collected;

[0020] Step 4: Neutralize the 61Cu eluate obtained in step 3 to pH 6–7 and evaporate to the target volume.

[0021] Preferably, in step 1, the heating temperature is 65-85 degrees Celsius.

[0022] Preferably, ZR resin is a 50-100 μm resin produced by Triskem, and AG1-X8 resin is a 100-150 μm resin produced by Bio-Rad.

[0023] Preferably, in step 2, activation is achieved using 12M HCl, and the chromatographic column is flushed with 2 column volumes of 12M HCl.

[0024] Preferably, in step 3, 8M HCl is used for equilibration; 3 times the column volume of 5M HCl is used for washing, and the column volume is equilibrated.

[0025] Preferably, 1 M NaOH is used for neutralization in step 4.

[0026] The Cu-61 separation and purification method based on multi-stage resin combination described in the present invention has the following technical advantages:

[0027] 1. Using the resin functional synergistic mechanism, ZR resin is used to treat GaCl4 based on the hydroxyoxime group. - With super selectivity and large adsorption capacity, AG1-X8 resin captures CuCl42 through anion exchange - CuCl3 - , combined with gradient elution to accurately separate Cu and Zn isotopes.

[0028] 2. By controlling the HCl concentration gradient, Cu and Ga are eluted step by step to avoid cross contamination, and the entire operation time is shortened to less than 2 hours.

[0029] 3. Use commercial resin combination, adapt to liquid / solid zinc targets and other irradiation targets to reduce production costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a schematic flow chart of a specific embodiment of the Cu-61 separation and purification method based on multi-stage resin combination according to the present invention;

[0031] Figure 2 Schematic diagram of the measured concentration of each isotope at each node in a specific embodiment of the present invention. DETAILED DESCRIPTION

[0032] The present invention will be further described in detail below with reference to the embodiments, but the present invention is not limited to the following embodiments:

[0033] The Cu-61 separation and purification method based on multi-stage resin combination of the present invention comprises the following steps:

[0034] Step 1. Target dissolution and pretreatment

[0035] After irradiation 64 The Zn target was placed in 10 mL of 12 M HCl and heated at 70 °C until completely dissolved. The undissolved particles were then removed by filtration to obtain a solution containing 61 Cu 2+ 、Zn 2+ 、Ga 3+ A clear solution of ions.

[0036] Step 2: ZR resin removes Ga impurities

[0037] The ZR resin was filled into the chromatographic column with a column bed volume of 3 mL and equilibrated to the Cl- type with 12 M HCl to activate the column. The clear solution obtained in step 1 was loaded at a flow rate of 1.2 mL / min so that the Ga 3+ The ions are adsorbed and the effluent is collected. The effluent contains Cu 2+ 、Zn 2+ ion.

[0038] Flush the column with 2 column volumes of 12M HCl to ensure Complete adsorption, discard the rinse solution; M represents the concentration in moles per liter;

[0039] In this step, under the condition of hydrochloric acid concentration ≥6M, Cu 2+ 、Zn 2+ 、Ga 3+ Reaction with hydrochloric acid to produce and ZR resin selective adsorption And Cu 2+ With Zn 2+ flow directly.

[0040] Step 3: Adsorption and elution of Cu by AG1-X8 resin

[0041] Fill a chromatographic column with AG1-X8 resin to a bed volume of 3 mL and equilibrate with 8 M HCl. Load the ZR resin effluent from step 2 onto the AG1-X8 column at a flow rate of 1.5 mL / min; then rinse with 3 column volumes of 5 M HCl and equilibrate the column volume.

[0042] Then, Cu was gradient eluted with 3M HCl at a flow rate of 0.5 mL / min, and the eluate containing 61Cu was collected;

[0043] In this step, AG1-X8 resin adsorbs the and By using a gradient elution of Cu 2+ Direct outflow to avoid cross contamination and recover high-purity 61Cu.

[0044] Step 4: Post-processing and quality control

[0045] Neutralize the 61Cu eluate obtained in step 3 to pH 6–7 with 1 M NaOH and concentrate by evaporation to the target volume.

[0046] Example 1: Verification of Ga removal efficiency of ZR resin in step 2

[0047] ZR resin was produced by Triskem (50–100 μm), and AG1-X8 resin was produced by Bio-Rad (100–150 μm). The chromatographic column had an inner diameter of 1.5 cm and a height of 10 cm.

[0048] 12M HCl solution was flowed into a 2mL ZR resin column at a flow rate of 1.2mL / min. The ion concentration of the effluent was detected by ICP-MS (inductively coupled plasma mass spectrometry). The Ga concentration in the effluent was <0.05ppm.

[0049] This indicates that the Ga adsorption rate is greater than 99.95%.

[0050] The recovery rates of Cu and Zn detected in the effluent were 98.2% for Cu and 99.8% for Zn, respectively.

[0051] Example 2: Optimization of AG1-X8 gradient elution in step 3

[0052] ZR resin was produced by Triskem (50–100 μm), and AG1-X8 resin was produced by Bio-Rad (100–150 μm). The chromatographic column had an inner diameter of 1.5 cm and a height of 10 cm.

[0053] Conditions: 8 M HCl → 5 M HCl gradient, AG1-X8 column volume 3 mL), flow rate 1.5 mL / min.

[0054] The Cu elution peak was concentrated in 3–4 column volumes, with a recovery of 96.5%.

[0055] ICP-MS detected the Zn residue to be 0.3 ppm.

[0056] Example 3: Full process

[0057] After input irradiation 64 Zn target (activity 10GBq 61 Cu).

[0058] Carry out step 2 and step 3 according to Example 1 and Example 2, respectively.

[0059] Final output 61 Cu activity: 9.2 GBq (92% recovery).

[0060] Detection of residual impurities: Ga 0.08ppm, Zn 0.5ppm.

[0061] Total time taken was 1.8 hours.

[0062] Confirmed by gamma spectroscopy 61 Cu characteristic peak, about 656keV, no characterization 68 The 511keV characteristic peak of Ga indicates that there is no 68 Ga interference. Detection by ICP-MS: Quantitative analysis of Zn and Ga residues, target value <1ppm.

[0063] In this embodiment, the reagent dosage and test results of each node are as follows: Step 1 is to mix 4 ml of each of the three solutions to simulate the 61 Cu 2+ 、Zn 2+ 、Ga 3+ A clear solution of ions. Node 1 simulates step 1. Nodes 2, 3, and 4 show the measurement results for step 2 when filling the sample with ZR resin and eluting with two 12M hydrochloric acid washes, each using 6 mL. Nodes 5 to 13 show the test results for step 3 using gradient elution, which employed three 8M hydrochloric acid washes, each 12 mL, and five 3M hydrochloric acid washes, each 6 mL. Negative test concentrations indicate values ​​below the detection limit of ICP-MS, and the actual concentration is assumed to be 0.

[0064]

[0065]

[0066]

[0067] like Figure 2 Given the measured concentrations of each isotope at the above 13 nodes, Figure 2 The horizontal axis represents the 13 nodes in the table, and the vertical axis represents the concentration. It can be seen that after step 2, the Zn concentration is greatly reduced, and after the gradient elution in step 3, a large amount of copper ions are retained in the solution. From the Zr resin column liquid to the 12M eluent, it can be seen that the Zn ion concentration is significantly eluted, while Ga is basically undetectable, indicating that it is completely retained on the Zr resin. From the A8 resin column liquid to the 5M hydrochloric acid eluent, no Cu ions are eluted, indicating that both Zn and Cu are well fixed to the A8 resin. Changing the acidity clearly shows that Cu ions are eluted, and the impurity content of Zn and Ga in the product is basically below 10 ppb, indicating that the elution process has a good separation effect on Cu and Ga / Zn.

[0068] The Cu-61 separation and purification method based on multi-stage resin combination described in the present invention has the following technical advantages:

[0069] 1. Adopting the resin functional synergistic mechanism, using ZR resin based on hydroxyoxime acid group to With super selectivity and large adsorption capacity, AG1-X8 resin captures Combined with gradient elution, Cu and Zn isotopes were accurately separated.

[0070] 2. By controlling the HCl concentration gradient, Cu and Ga are eluted step by step to avoid cross contamination, and the entire operation time is shortened to less than 2 hours.

[0071] 3. Use commercial resin combination, adapt to liquid / solid zinc targets and other irradiation targets to reduce production costs.

[0072] The above content is a further detailed description of the present invention in conjunction with specific preferred embodiments, and the specific embodiments of the present invention cannot be considered to be limited to these descriptions. For those skilled in the art to which the present invention belongs, other embodiments derived without departing from the technical solution of the present invention should be included in the scope of protection of the present invention.

Claims

1. A Cu-61 separation and purification method based on multi-stage resin coupling, characterized in that: The steps include: Step 1. Target dissolution and pretreatment After irradiation 64 The Zn target was placed in HCl and heated until completely dissolved, and then the undissolved particles were removed by filtration to obtain 61 Cu 2+ 、Zn 2+ 、Ga 3+ clear solution of ions; Step 2: ZR resin removes Ga impurities The ZR resin was filled into the chromatographic column and activated with 6-12M HCl; the clear solution obtained in step 1 was loaded so that the Ga 3+ The ions are adsorbed and the effluent is collected. The effluent contains Cu 2+ 、Zn 2+ ion; Flush the column to ensure GaCl4 - Complete adsorption; M represents the concentration in moles per liter; Step 3: Fill the AG1-X8 resin into the chromatographic column and equilibrate with 5 to 10 M HCl; load the ZR resin effluent obtained in step 2 into the AG1-X8 column, then rinse and equilibrate the column volume; Then, Cu was eluted by gradient elution with HCl from 3 to 5 M, and the eluted elution containing 61 Cu eluent; Step 4: Neutralize the solution obtained in step 3 61 The Cu eluate was adjusted to pH 6–7 and concentrated by evaporation to the target volume.

2. The Cu-61 separation and purification method based on multi-stage resin coupling according to claim 1, characterized in that: In step 1, the heating temperature is 65-85 degrees Celsius.

3. The Cu-61 separation and purification method based on multi-stage resin coupling according to claim 1, characterized in that: ZR resin is a 50–100 μm resin produced by Triskem, and AG1-X8 resin is a 100–150 μm resin produced by Bio-Rad.

4. The Cu-61 separation and purification method based on multi-stage resin coupling according to claim 1, characterized in that: In the step 2, activation is achieved using 12 M HCl, and the chromatographic column is flushed with 2 column volumes of 12 M HCl.

5. The Cu-61 separation and purification method based on multi-stage resin coupling according to claim 1, characterized in that: In step 3, 8 M HCl was used for equilibration; 3 times the column volume of 5 M HCl was used for washing, and the column volume was equilibrated.

6. The Cu-61 separation and purification method based on multi-stage resin combination according to claim 1, characterized in that: In step 4, 1 M NaOH was used for neutralization.

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