A method, system, and product for the preparation of high purity copper-64 isolated and purified from a nickel target

Abstract

This invention discloses a method, system, and product for separating and purifying high-purity copper-64 from a nickel target, belonging to the field of radionuclide preparation and separation technology. The method includes acid dissolution of the irradiated nickel target, and the resulting product containing... 64 Cu、 64 Ni、 61 The solution of Co was loaded onto a pretreated AG1-X8 anion exchange resin column, followed by rinsing with 50-60 mL of 6M HCl to remove Co. 64 Ni was removed by rinsing with 20-30 mL of 4M HCl. 61 Co was finally eluted with 4-6 mL of 2M HCl to obtain high purity. 64 Cu product. This invention achieves highly efficient and selective separation of 64Cu by optimizing the elution sequence and conditions. The product has a nuclear purity >99.9%, extremely low content of key metal impurities, and a separation efficiency of over 84%, making it suitable for medical applications. 64 A reliable solution has been provided for the large-scale production of Cu.

Description

Technical Field

[0001] This application belongs to the field of radioisotope preparation and radiochemical separation technology, specifically involving the preparation method, system and product for separating and purifying high-purity copper-64 from a nickel target. Background Technology

[0002] Copper-64 ( 64 Cu is a promising medical positron emitter with a 12.7-hour half-life, making it ideal for positron emission tomography (PET) diagnostics and potential targeted radiotherapy research. 64 Cu is typically enriched by proton bombardment in a cyclotron. 64 Ni sputtering material, via 64 Ni(p,n) 64 Cu nuclei are generated. After bombardment, the target material contains the target product. 64 Besides Cu, there are also a large number of unreacted substances. 64 Ni and by 64 Ni(p,α) 61 Side reactions such as Co produce 61 Radioactive impurities such as Co. These impurity nuclides not only dilute the radioactive material... 64 The specific activity of Cu affects imaging quality and treatment efficacy, including stable metal ions such as Ni. 2+ Co 2+ This can interfere with subsequent bioconjugation labeling reactions and even introduce toxic side effects. Therefore, the efficient and selective separation of high radiochemical purity and high specific activity from the solution is crucial. 64 Cu is a key prerequisite for its clinical application.

[0003] Currently, anion exchange chromatography is the method for separating... 64 The mainstream technology of Cu utilizes 64 Cu 2+ CuCl3 can be formed in concentrated hydrochloric acid. - CuCl4 2- The principle is that the complexed anions are strongly adsorbed by anion exchange resins (such as AG1-X8), causing them to react with Ni, which exists in hydrochloric acid as a cation. 2+ Separation. Traditional methods often involve loading the sample with high-concentration hydrochloric acid (such as 9-12M HCl) and washing to remove nickel, followed by elution with low-concentration acid or water. 64 Cu. However, this method has operational hazards (high concentration of acid) and cobalt impurities ( 61 Co) Incomplete removal 64 Cu elution peak tailing can lead to problems such as large product volume and low concentration. Therefore, it is necessary to develop a method with optimized steps, mild conditions, and the ability to effectively remove both nickel and cobalt impurities simultaneously. 64The separation and purification process of Cu with high concentration and narrow peak elution is of great significance. Summary of the Invention

[0004] The purpose of this invention is to provide a method, system, and product for separating and purifying high-purity copper-64 from a nickel target, which can effectively solve the problems in the background art mentioned above.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for separating and purifying high-purity copper-64 from a nickel target, comprising the following steps: S1: Acid dissolution of a nickel target irradiated by a cyclotron yields a solution containing... 64 Cu、 64 Ni and 61 Acidic solution of Co; S2: Pre-treat the AG1-X8 anion exchange resin and pack it into a column to obtain a separation column for use; S3: Load the solution obtained in step S1 onto the separation column; S4: Elute the separation column with a first preset volume of 6M hydrochloric acid to elute and remove [the pollutants]. 64 Ni impurities; S5: Elute the separation column treated in step S4 with a second preset volume of 4M hydrochloric acid to remove elution and residue. 61 Co impurities; S6: Elute the separation column treated in step S5 with a third preset volume of 2M hydrochloric acid, collect the eluent, and obtain high-purity eluent. 64 Cu products.

[0006] Preferably, the first preset volume in step S4 is 50-60 mL; the second preset volume in step S5 is 20-30 mL; and the third preset volume in step S6 is 4-6 mL.

[0007] Preferably, in step S4, during the 6M hydrochloric acid rinsing step, 64 Ni impurities are concentrated in the first 20 mL of eluent; when the eluent volume reaches 50-60 mL, the impurities in the effluent decrease. 64 Ni concentration is below 10 ppb.

[0008] Preferably, in step S6, during the 2M hydrochloric acid rinsing step, 64 Cu products are concentrated in fractions 2 through 6 of this step.

[0009] Preferably, the method further includes an efficiency evaluation, wherein the product separation efficiency is calculated according to formula (1) under cold experimental conditions: (1) in, The concentration of Cu ions in the product is expressed in ppb. The volume of product collected is in mL. The total mass of Cu added to the column electrolyte is expressed in μg.

[0010] Preferably, the method further includes an efficiency evaluation, wherein the total separation efficiency is calculated according to formula (2) under thermal experimental conditions: (2) in, In the column liquid 64 Initial radioactivity of Cu, in mCi; To separate and purify the product 64 The radioactivity of Cu, expressed in mCi.

[0011] Preferably, it also includes the obtained 64 Cu products undergo quality verification, with their nuclear purity determined using a high-purity germanium gamma-ray spectrometer, and the purity must be >99.9%. Their half-life is measured by examining the activity at different time points. According to the radioactive decay equation The fitting was validated, and the calculated half-life was obtained. It must meet the requirement of 12.7 ± 0.2 hours.

[0012] The present invention also provides a copper-64 separation and purification system for implementing any of the methods described above, characterized in that it comprises: Dissolution unit, used to dissolve the irradiated nickel target; The chromatographic separation unit has a built-in separation column containing AG1-X8 resin; The rinsing solution supply unit stores and delivers 6MHCl, 4MHCl, and 2MHCl. The flow control and collection unit controls the liquid flow direction and collects the outflow liquid in segments. The control unit is programmed to control the system to sequentially perform 6MHCl rinsing, 4MHCl rinsing, and 2MHCl rinsing.

[0013] The present invention also provides a high-purity copper-64 radionuclide product, prepared by any of the methods described above, wherein the product has a nuclear purity of more than 99.9%, and the content of residual key metal impurities therein meets the following requirements: Ni < 0.005 μg / GBq, Co < 0.001 μg / GBq.

[0014] This application also provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the method described in any of the foregoing claims or controls the operation of the system described above.

[0015] Compared with the prior art, the present invention has the following beneficial effects: This invention employs a three-stage elution strategy of "washing Ni with 6MHCl, washing Co with 4MHCl, and washing Cu with 2MHCl" to specifically remove different impurities. 64 The Cu recovery rate is high, and the overall separation efficiency can reach 84.4%.

[0016] The maximum acid concentration used in this invention is 6MHCl, which is safer and less corrosive to equipment than the 9-12MHCl used in traditional methods.

[0017] The 4M HCl elution step added in this invention effectively removes... 61 Co, combined with optimized rinsing volume, makes 64 Cu products have a purity of >99.9%, and the content of key metal impurities is far below the industry standard.

[0018] This invention clarifies the efficiency calculation formula and the mathematical model for quality verification (such as the half-life verification formula), enabling the process and product quality to be quantitatively evaluated and controlled.

[0019] Suitable for automated production: The steps are clear, the parameters are well-defined, and it is easy to integrate into automated synthesis modules, meeting clinical-grade requirements. 64 The need for large-scale and standardized production of Cu. Attached Figure Description

[0020] Figure 1 This is an overall process flow diagram of the separation and purification method of the present invention, illustrated according to an exemplary embodiment; Figure 2 This is a schematic diagram of the Ni ion elution curve of the separation and purification method of the present invention, according to an exemplary embodiment; Figure 3 The present invention's separation and purification method, illustrated in an exemplary embodiment, involves eluting Cu with HCl of varying concentrations. 2+ Product illustration; (a) is 0.1M HCl; (b) is 1M HCl; (c) is 1.5M HCl; and (d) is 2M HCl. Figure 4 This is a schematic diagram illustrating the concentration of each stream of Co2+ eluted by MHCl according to an exemplary embodiment of the present invention. Where (a) is Co 2+ Concentration; (b) is Ni 2+ Concentration; (c) is Cu 2+ concentration; Figure 5 This is a schematic diagram of the thermal elution product curve of the separation and purification method of the present invention, according to an exemplary embodiment; Figure 6 This is an example of the separation and purification method of the present invention shown in an exemplary embodiment. 61 Schematic diagram of the product tested by the Co-plated high-purity germanium gamma spectrometer; Figure 7 Measurement of the separation and purification method of the present invention according to an exemplary embodiment. 64 A schematic diagram of the equation fitted on a logarithmic scale to show the relationship between the activity of Cu products at different time points and time. Detailed Implementation

[0021] Exemplary embodiments will now be described in detail, examples of which are illustrated in the accompanying drawings. When the following description relates to the drawings, unless otherwise indicated, the same numbers in different drawings denote the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Rather, they are merely examples consistent with some aspects of the invention as detailed in the appended claims.

[0022] Example 1: Separation and Purification Method This embodiment details the separation and purification of high-purity nickel from a nickel target. 64 The Cu method, the overall process is as follows: Figure 1 As shown.

[0023] S101: Acid dissolution of the target material. After the metallic nickel target has been irradiated by a cyclotron for approximately 3 hours, it is removed from the target holder and dissolved using one of the following two methods: Method A: Transfer the target material to a round-bottom flask and add 2 mL of 6M HCl. Install a reflux condenser and heat under reflux in an oil bath at 110°C for at least 1 hour until the nickel target is completely dissolved, the solution is clear, and no obvious bubbles are generated.

[0024] Method B: Transfer the target material to a round-bottom flask, add 3-5 mL of 12M HCl and 2 mL of 30% hydrogen peroxide (H2O2). Heat at 110°C for 1 hour until completely dissolved, then evaporate the solution to dryness under heating. Add 2 mL of 6M HCl to the residue and gently shake to completely redissolve it.

[0025] Regardless of the method used, approximately 2 mL of 6M HCl solution containing the target product was ultimately obtained. 64 Cu, large amount of unreacted 64 Ni and by 64 Ni(p,α) 61 Nuclear reactions such as Co produce 61 Impurities such as Co.

[0026] S102: Preparation and pretreatment of AG1-X8 resin columns.

[0027] a) Column pretreatment: Rinse the polypropylene resin column and hydrophilic sieve plate with a large amount of ultrapure water to remove particulate impurities. Then rinse with a small amount of 0.1M HCl, and finally immerse the column and sieve plate in 0.1M HCl solution for more than 24 hours.

[0028] b) Resin swelling: Weigh approximately 9 g of AG1-X8 anion exchange resin using a precision electronic balance and place it in a 50 mL centrifuge tube. Add 20 mL of 0.1 M HCl, shake for 10 minutes, let stand for 5 minutes, and then discard the supernatant. Subsequently, add 20 mL of 6 M HCl, shake to mix, and allow the resin to swell in the 6 M HCl medium for at least 12 hours.

[0029] c) Column Packing and Equilibration: Install the hydrophilic sieve plate at the bottom of the column and inject a small amount of 6MHCl to expel air bubbles below the sieve plate. Close the column outlet and transfer all the swollen resin slurry into the column. Open the outlet and allow the liquid to flow out slowly under gravity, keeping the liquid level above the top of the resin bed throughout the process to prevent air bubbles from entering. After the resin settles naturally to form a uniform bed, install the upper sieve plate on top and lightly compact it. Finally, fill the column cavity with 6MHCl, seal the inlet and outlet, and set aside for later use.

[0030] S103: Sample loading and adsorption. Approximately 2 mL of the solution prepared in S101 is loaded onto an AG1-X8 resin column equilibrated with 6M HCl at a flow rate of 0.5-1 mL / min. Under these conditions, 64 Cu 2+ With high concentration of Cl - Stable chloride complex anions are formed and strongly adsorbed by the resin; while 64 Ni 2+ It still exists mainly in the form of cations in concentrated hydrochloric acid, and is not adsorbed by the resin or is only weakly adsorbed. Most of it passes directly through with the liquid flow.

[0031] S104: 64 Ni impurity elution. After sample loading, elute the resin column with 50-60 mL of 6M HCl at a constant flow rate. This step aims to thoroughly elute any breakthrough or weakly adsorbed impurities. 64 Ni 2+ The rinsing process can employ segmented collection. Among these, 64 Ni 2+ The concentration is high in the first 20 mL of eluent. When the cumulative eluent volume reaches 50-60 mL, the concentration in the effluent... 64 The Ni concentration is below 10 ppb, meeting the stringent requirements for impurity content in medical radionuclides. Collect this entire eluent as a sample containing... 64 Ni waste liquid. Experimental monitoring showed that during this 6M HCl rinsing stage, 64 Cu is firmly adsorbed onto the column with virtually no loss.

[0032] S105: 61 Co impurities are eluted. The receiving container is replaced, and the resin column is further eluted with 20-30 mL of 4M HCl. This step is one of the key optimizations of this invention, designed to elute impurities that were not completely removed under 6M HCl conditions, and whose chlorine complex behavior may be related to… 64 Cu-like 61 Co impurities. 61 Co was eluted in large quantities in this 4M HCl elution section. This portion of the eluent was collected as a solution containing Co. 61 Co waste liquid. This step can effectively avoid 61 Co is mixed into the final product to ensure the product's nuclear purity.

[0033] S106: 64 Cu product elution. The product collection bottle was replaced again with a calibrated one, and the resin column was eluted with 4-6 mL of 2M HCl. Through systematic research on the elution effect of different concentrations of HCl (0.1M, 1M, 1.5M, 2M), 2M HCl was determined to be the optimal elution concentration. Figure 3 As shown, at this concentration, 64 Cu was eluted efficiently, with sharp, symmetrical, and concentrated elution peaks, and no tailing phenomenon. Product 64Cu The eluent is mainly concentrated in fractions 2 through 6 of this step, with a total volume of approximately 4-6 mL. Collecting this eluent yields a fraction with high radiochemical purity and high specific activity. 64 CuCl2 hydrochloric acid solution product.

[0034] Example 2: Efficiency Calculation and Product Quality Verification Method This embodiment details the evaluation of the separation and purification efficiency of the method described in Example 1 and the final... 64Cu Product quality verification methods.

[0035] Cold experiment separation efficiency calculation: During the process verification under non-radioactive conditions (cold experiment), a known mass of stable Cu element (m0) was added to the simulated solution. After purification, the concentration of Cu ions in the product solution was measured. (Unit: ppb) and volume of product liquid (Unit: mL). The elemental separation efficiency under cold experimental conditions was calculated using formula (1): (1) Under optimized process conditions, this efficiency can approach 100%, indicating that the chemical recovery rate of Cu is close to complete.

[0036] Calculation of separation efficiency in thermal experiments: In actual radioactive separation (thermal experiments), it is necessary to evaluate... 64 Radiochemical recovery rate of Cu nuclides. Precise measurements were taken of the concentration of Cu in the solution before column loading.64 Initial radioactivity of Cu (Unit: mCi) and the final product after separation and purification 64 Radioactivity of Cu (Unit: mCi). The total radiochemical separation efficiency is calculated using formula (2): (2) Using the optimized process of this invention (washing Ni with 6MHCl, washing Co with 4MHCl, and washing Cu with 2MHCl), thermal experiments show that... 64 The overall separation efficiency of Cu can reach over 84.4%, demonstrating the high efficiency of the process.

[0037] 64 Cu product quality verification: a) Nuclear purity analysis: The product solution was analyzed using a high-purity germanium gamma-ray spectrometer. In qualified products, 64 Cu has prominent characteristic peaks, and there should be no [specific peaks] in the spectrum. 61 Characteristic γ-peaks of impurity nuclides such as Co. The product obtained by the method of this invention has a nuclear purity higher than 99.9%.

[0038] b) Half-life verification: Accurately measure the radioactivity of the product at multiple different decay time points t. According to the exponential decay law of radionuclides, their activity changes over time according to the formula... ,in Initial activity, Let be the decay constant. For With time By performing a linear fit, the slope of the resulting straight line is... Then, through the formula Calculate this batch 64 The half-life of Cu products. It has been verified that the Cu prepared by the method of this invention... 64 Cu products, half-life The decay time was 12.70 hours, which is within the theoretical range of 12.7 ± 0.2 hours, thus confirming the high nuclide purity of the product from the decay characteristics.

[0039] c) Determination of metal impurity content: to be determined 64 After the Cu product has completely decayed, the concentration of residual stable metal impurities in the solution was determined using inductively coupled plasma mass spectrometry (ICP-MS) and converted to per GBq. 64The impurity mass (μg / GBq) corresponding to Cu activity. The key metal impurity content of the product of this invention is extremely low, meeting the following requirements: Ni < 0.005 μg / GBq, Co < 0.001 μg / GBq, Fe < 0.127 μg / GBq, Zn < 0.126 μg / GBq, which is far superior to the industry-recognized quality control standards.

[0040] Specifically, 64 Cu and 64 When Ni is separated using AG1-X8 resin, the first step is elution. 64 6MHCl is used in the Ni process for the recovery of raw materials and the removal of impurities.

[0041] exist Figure 2 During elution, we collected different fractions in segments. The first and second samples were each 10 mL (corresponding to the first 20 mL of eluent), while the third and subsequent samples were each 5 mL. The analytical results showed that Ni... 2+ The highest concentration of Ni was found in the first two samples during the initial elution phase (i.e., the first 20 mL of elution waste liquid). This portion of the solution can be used as Ni... 2+ The recovered solution is collected. As the elution volume increases, Ni... 2+ The concentration decreased rapidly, and by the 10th sample (corresponding to an elution volume of 55-60 mL), the concentration had fallen below 10 ppb, completely eliminating the need for subsequent applications of Ni. 2+ The stringent requirements regarding residues will not affect the product's specific activity or subsequent labeling effectiveness. Therefore, eluting Ni... 2+ The process can be terminated after this volume, without further elution. As shown in Table 1, Cu was not detected in the first three eluted samples. 2+ This phenomenon may be due to Ni 2+ Too high a concentration or too high a dilution factor leads to Cu 2+ The signal was too weak to be detected. Looking at the overall results of the cold experiment, Cu... 2+ The fact that almost no loss occurred indicates that the removal of Ni... 2+ The process for Cu 2+ The retention rate was relatively ideal. To further verify the separation effect of this method under actual radioactive conditions, further thermal experiments are needed to test the product. 64 Cu 2+ The radioactivity level is measured to confirm whether there is any loss of the target nuclide.

[0042] Table 1 Ni 2+ Cu in the waste liquid during elution 2+ Concentration change

[0043] To determine Cu 2+To determine the optimal elution concentration for the product, we investigated the elution effects of different concentrations of HCl (0.1M, 1M, 1.5M, and 2M). Experimental conditions: 2 mL per fraction; the initial loading solution contained 120 mg Ni and 15... gCu. Elution curve as shown Figure 3 As shown, by analyzing the Cu of each flow fraction 2+ Evaluate elution efficiency by analyzing concentration changes and total mass recovery.

[0044] Cu was eluted with 0.1M HCl. 2+ The elution curve shows a slow upward trend: Cu in the first 8 fractions 2+ The concentration was extremely low, rising sharply from the 9th fraction, reaching its peak in the 10th fraction, and then gradually decreasing. The peak shape was broad and flat with severe tailing, and the elution process lasted for more than 12 fractions. Based on mass balance, only about 60% Cu was present. 2+ Eluted, large amount of Cu 2+ The residue remaining on the column indicates that the elution power of 0.1M HCl is insufficient and cannot effectively compete with Cu. 2+ Binding sites with the stationary phase.

[0045] Increasing the HCl concentration to 1M significantly improved the elution curve. 2+ Rapid elution begins from the fourth fraction, reaching its peak in the sixth fraction. The peak shape is more concentrated and sharper than that of 0.1M HCl, with reduced tailing. The elution cycle is shortened to approximately 10 fractions. Cu 2+ Recovery increased to approximately 85%, with a significant reduction in column residue. This indicates that increasing Cl... - Increased concentration with Cu 2+ The coordination competition promotes its desorption from the column.

[0046] When the HCl concentration increased to 1.5 M, the elution efficiency further improved. 2+ The elution peak shifts forward to the third fraction and begins to rise rapidly, reaching its peak in the fifth fraction. The peak shape becomes more symmetrical and sharper, and the tailing almost disappears. The elution process is basically completed within nine fractions. Cu 2+ Recovery rate exceeds 90%, with minimal residue on the column. At this concentration, high-concentration Cl... - For Cu 2+ The coordination effect of Cu is dominant, making Cu 2+ The affinity with the stationary phase is significantly reduced.

[0047] The elution effect is optimal under 2M HCl conditions. Cu 2+ Elution began rapidly from the second fraction, reaching a sharp peak in the fourth fraction. The peak shape was highly concentrated and symmetrical, with no visible tailing. The entire elution process was completed within eight fractions, the shortest of all groups. Mass calculations showed that Cu... 2+With a recovery rate approaching 100% and virtually no residue on the column, Cu was achieved. 2+ Completely washed away.

[0048] Combining the results from the four groups, as the HCl concentration increased from 0.1M to 2M, Cu 2+ The elution behavior exhibits a regular pattern: the elution peak gradually shifts forward, the peak width narrows, the peak shape changes from flat to sharp, the tailing is reduced, and the recovery rate increases. This trend is attributed to high concentrations of Cl. - With Cu 2+ Formation of stable chloride complexes (such as CuCl4) 2- ), significantly weakening Cu 2+ The interaction between Cu and the stationary phase accelerates elution and improves desorption completeness. Among these, 2M HCl showed the most concentrated, rapid, and complete elution with the highest recovery rate, indicating that this concentration is sufficient to overcome Cu... 2+ The adsorption on the column is Cu 2+ The optimal concentration for product elution can be determined by using 2M HCl as the elution condition in subsequent experiments to ensure efficient recovery.

[0049] The 2MHCl elution product is mainly concentrated in the 5th and 6th fractions, which can be used as the final product and then verified through thermal experiments.

[0050] Co 2+ Elution conditions study Multiple parallel experiments were designed to verify the separation effect: 6M HCl was split into two fractions at 40 mL and 50 mL; 4M HCl was split into four fractions, each with a volume of 5 mL; and 2M HCl was split into two fractions with a volume of 2 mL.

[0051] like Figure 4 As shown in (a), Ni was eluted with 6M HCl. 2+ During the process, Co 2+ There was some premature elution. High concentrations of Co were detected in the first two fractions. 2+ This indicates that some Co 2 As you wish 2+ They were eluted together; after entering the 4M HCl elution stage, Co 2+ It was eluted extensively, and its concentration rose rapidly from 60 ppb in the third fraction to a peak in the fifth fraction, after which it began to decline; during the elution phase with 2M HCl, Co 2+ When the concentration reaches below 20 ppb, it indicates that elution is close to complete.

[0052] For Ni 2+The elution behavior of Ni was previously shown in experiments to require at least 50 mL of 6M HCl for complete elution. Considering that when using a wet column method, at least 2 mL of HCl remains in the resin column at all times, to balance separation efficiency and reagent usage, subsequent experiments will focus on using only 50 mL of 6M HCl for Ni elution. 2+ Washing. For example... Figure 4 As shown in b, in the last two fractions of 6M HCl, Ni 2+ The concentration remained high, but in the subsequent 4M HCl fraction, Ni... 2+ The content continued to decrease and stabilized below 20 ppb, which would not cause contamination to the target product, indicating that the elution conditions were feasible in actual operation.

[0053] like Figure 4 As shown in (c), Cu 2+ The monitoring results showed that Ni was eluted with 6M HCl. 2+ Cu was not observed in the stage 2+ The loss indicates that Cu in this stage 2+ It was well retained. However, in the fourth 4M HCl fraction, Cu... 2+ Losses began to occur, possibly due to excessive elution volume leading to some Cu being lost. 2+ The column is not firmly attached, or 4M HCl reacts with Cu. 2+ It exhibits some elution effect. It is worth noting that Cu... 2+ The fractions were mainly enriched in the 5th and 6th fractions. Further thermal experiments will be conducted to evaluate the activity loss and confirm the separation stability under actual operating conditions.

[0054] After optimization, the thermal experiment involved irradiation with an 11MeV medical cyclotron for 3 hours. Following a series of processes including dissolution, transport, separation, and purification, the activity of each fraction was measured. Figure 5 As shown. The dissolution-transfer efficiency was 97%, indicating that the liquid lost during dissolution-transfer had virtually no impact on the activity; the overall purification efficiency reached 84.4% after elution with 6M HCl. 64 The loss of 25.7 mCi (6.65%) in Ni impurities was observed during elution with 4 M HCl. 61 8.8 mCi (2.27%) was lost in Co, with the majority of the loss occurring in the first discarded product bottle.

[0055] To comprehensively evaluate the production 64 The mass of Cu nuclides was systematically determined in this study, including their metal impurity content and half-life. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze the mass. 64Quantitative analysis was performed on the residual metallic impurities after the complete decay of the Cu solution, and the results are shown in Table 2-7. The data shows that the concentrations of key metallic impurities such as Ni, Co, Fe, and Zn are all at extremely low levels (specific values ​​are shown in Table 2), far below the industry-recognized permissible limits, indicating that this production process has excellent removal efficiency for both non-radioactive and radioactive metallic impurities. Simultaneously, high-purity germanium gamma spectroscopy was used to further analyze... 64 Analysis of CuCl2 solution ( Figure 6 ), 64 Cu radionuclide purity > 99.9%; 64 The half-life of Cu was determined by measuring the product activity at different time points using the following equation:

[0056]

[0057]

[0058] in for 64 Cu in Radioactivity at any given time for 64 Radioactivity of Cu at time 0 It is a constant. Measurements were taken at different time points. 64 The activity of Cu products, fitted on a logarithmic scale (image) Figure 7 The following equation is derived:

[0059] When t = T1 / 2, A = 0.5A0

[0060] Calculate 64 The half-life of Cu is:

[0061] Calculation of product 64 The half-life of Cu is 12.6996 h and its isotopes 64 The half-life of Cu was consistent with 12.7 h, further confirming the purity of the nuclide. Based on the combined results of metal impurity analysis, gamma spectroscopy identification, and half-life determination, the produced... 64 Cu products are of excellent quality and fully meet the application requirements of high-purity radiopharmaceuticals.

[0062] Table 2 64 The residual metal ion concentration after complete decay of Cu solution

[0063] Example 3: This example provides an automated or semi-automated separation and purification system for implementing the above method, aiming to improve production repeatability, efficiency, and operational safety. The system includes: Dissolution heating module: used for programmed temperature-controlled heating and dissolution of the irradiated nickel target.

[0064] AG1-X8 resin chromatography column module: the core separation unit.

[0065] Eluent supply module: contains multiple sealed reagent bottles, which store solutions such as ultrapure water, 0.1M HCl, 6M HCl, 4M HCl, and 2M HCl respectively, and are supplied with delivery pressure by an inert gas (such as Ar) or connected to a pump.

[0066] Flow path control and transfer module: Composed of a multi-port selector valve, a precision injection pump or plunger pump, and corrosion-resistant tubing (such as PEEK tubing), it is used to precisely control the flow of samples and different eluents through the resin column in a preset order and at a preset flow rate.

[0067] Automatic fraction collection module: A programmable fraction collector used to automatically collect fractions containing [specific components] in a step-by-step manner. 64 Ni waste liquid, containing 61 Co's waste liquid and final 64 Cu product liquid.

[0068] Control Module: Equipped with a built-in Programmable Logic Controller (PLC) or industrial computer, this module executes the following automatic control sequence: First, it drives the system to equilibrate the resin column with 6M HCl; then, it controls the loading of the sample solution; next, it sequentially drives a 6M HCl rinse (preset volume 50-60 mL) and triggers the collector to collect the first waste liquid; then, it drives a 4M HCl rinse (preset volume 20-30 mL) and collects the second waste liquid; finally, it drives a 2M HCl rinse (preset volume 4-6 mL) and collects the effluent into the product bottle. This system can record parameters for each step, achieving automated operation and recording of the process flow.

[0069] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the appended claims.

Claims

1. A method for preparing high-purity copper-64 from a nickel target, characterized in that, Includes the following steps: S1: Acid dissolution of a nickel target irradiated by a cyclotron yields a solution containing... 64 Cu、 64 Ni and 61 Acidic solution of Co. S2: Pre-treat the AG1-X8 anion exchange resin and pack it into a column to obtain the separation column for use. S3: Load the solution obtained in step S1 onto the separation column. S4: Elute the separation column with a first preset volume of 6M hydrochloric acid to elute and remove [the pollutants]. 64 Ni impurities S5: Elute the separation column treated in step S4 with a second preset volume of 4M hydrochloric acid to remove elution and residue. 61 Co impurities, S6: Elute the separation column treated in step S5 with a third preset volume of 2M hydrochloric acid, collect the eluent, and obtain high-purity eluent. 64 Cu products.

2. The method according to claim 1, characterized in that, In step S4, the first preset volume is 50-60 mL; in step S5, the second preset volume is 20-30 mL; and in step S6, the third preset volume is 4-6 mL.

3. The method according to claim 1 or 2, characterized in that, In step S4, during the 6M hydrochloric acid rinsing step, 64 Ni impurities are concentrated in the first 20 mL of eluent; when the eluent volume reaches 50-60 mL, the impurities in the effluent decrease. 64 Ni concentration is below 10 ppb.

4. The method according to claim 1, characterized in that, In step S6, during the 2M hydrochloric acid rinsing step, 64 Cu products are concentrated in fractions 2 through 6 of this step.

5. The method according to claim 1, characterized in that, The method also includes an efficiency evaluation, whereby the product separation efficiency is calculated according to formula (1) under cold experimental conditions: （1）, in, This represents the Cu ion concentration in the product, expressed in ppb. Product collection volume, in mL. The total mass of Cu added to the column electrolyte is expressed in μg.

6. The method according to claim 1, characterized in that, The method also includes an efficiency evaluation, whereby the total separation efficiency is calculated according to formula (2) under thermal experimental conditions: （2）, in, In the column liquid 64 Initial radioactivity of Cu, in mCi. To separate and purify the product 64 The radioactivity of Cu, expressed in mCi.

7. The method according to claim 1, characterized in that, Also includes the income 64 Cu products undergo quality verification, with their nuclear purity determined using a high-purity germanium gamma-ray spectrometer, requiring a purity >99.9%. Their half-life is determined by measuring the activity at different time points. According to the radioactive decay equation The fitting was validated, and the calculated half-life was obtained. It must meet the requirement of 12.7 ± 0.2 hours.

8. A copper-64 separation and purification system for implementing the method of any one of claims 1-7, characterized in that, include: Dissolution unit, used to dissolve the irradiated nickel target. The chromatographic separation unit contains a separation column filled with AG1-X8 resin. The rinsing solution supply unit stores and delivers 6MHCl, 4MHCl, and 2MHCl. The flow path control and collection unit controls the liquid flow direction and collects the outflow liquid in stages. The control unit is programmed to control the system to sequentially perform 6MHCl rinsing, 4MHCl rinsing, and 2MHCl rinsing.

9. A high-purity copper-64 radionuclide product, characterized in that, The product is prepared by the method described in any one of claims 1-7, and the purity of the product is higher than 99.9%, and the content of residual key metal impurities therein satisfies: Ni < 0.005 μg / GBq, Co < 0.001 μg / GBq.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by a processor, it implements the method as described in any one of claims 1-7, or controls the operation of the system as described in claim 8.

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