A method for separating 89 Zr from a yttrium target and applications

Abstract

This invention provides a method for separating on a yttrium target 89 The method for Zr includes the following steps: (1) containing 89 (2) The Zr target was cooled, dissolved, and filtered; (3) the solution obtained in step (1) was separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent was collected; (4) the eluent obtained in step (2) was separated again using column chromatography or solution extraction, washed and eluted with hydrochloric acid, and the second eluent was collected to obtain purified Zr. 89 Zr. This method uses resin impregnation and solvent extraction to... 89 Zr can be separated; the resin impregnation method can be highly automated during use, reducing the radiation dose to personnel; the solvent extraction method can shorten the separation time and ensure... 89 Zr activity is reduced, decreasing radiation exposure for workers in the environment. This invention also provides methods for separating Zr on a yttrium target using this method. 89 Application of Zr in radioimmunotherapy drugs.

Description

Technical Field

[0001] This invention relates to the technical field of radioactive isotope purification, and in particular to a method for separating radioactive isotopes on a yttrium target. 89 Zr methods and applications. Background Technology

[0002] Medical radionuclide Zr-89 (zirconium-89, 89 Zirconium-89 (Zr-89) is frequently used to visualize and quantify the uptake of monoclonal antibodies (mAbs) because its half-life of 3.3 days makes it ideal as a biomarker for PET imaging to evaluate the expression of target proteins and the tumor targeting of monoclonal antibodies. Therefore, Zr-89 is an important research tool for many research institutions, research hospitals, and pharmaceutical companies interested in protein imaging or therapy. For example, some researchers have used it... 89 Zr-labeled pembrolizumab was then used in positron emission tomography (PET) imaging studies to understand the optimal timing of PET scans and the uptake of pembrolizumab.

[0003] It is evident that, at different stages of drug development, based on 89 ImmunoPET imaging of Zr radionuclides has always been an attractive imaging method, specifically for screening lead compounds, preclinical imaging, and translating mouse model results into human models.

[0004] 89 Zr is generally isolated from yttrium targets and then used in clinical applications, which requires ensuring... 89 Zr needs to be present in a suitable quantity to produce sufficient activity. Traditional methods for isotope separation include chemical separation, ion exchange chromatography, gas diffusion, laser separation, and centrifugation. For example, chemical separation utilizes the differences in the physicochemical properties of the substances to be separated. However, in practical applications, it often has poor selectivity and can only be used for crude purification. It also needs to be used in conjunction with other separation methods to obtain the target product. For substances with decay characteristics... 89 Zr is not suitable. Moreover, the separation methods mentioned above generally suffer from problems such as long process flow, difficulty in eluting the product, and excessively high elution acidity.

[0005] because 89 The complexity of the Zr production process and its time-degradation characteristics make it difficult to isolate high-abundance Zr from yttrium targets for medical use. 89 Zr is relatively difficult. Therefore, in order to... 89 To separate and enrich Zr from a yttrium target, those skilled in the art need to develop a rapid separation method with high separation performance and high end product abundance. Summary of the Invention

[0006] To address the aforementioned problems in the existing technology, the present invention provides a method for separating on a yttrium target. 89 The Zr method, using resin impregnation and solvent extraction methods, 89 Zr separation is performed; among these methods, resin impregnation can be highly automated, reducing human radiation exposure; solvent extraction can significantly shorten the separation time and maximize the preservation of Zr. 89 This invention also reduces the radiation exposure of workers in the environment by increasing Zr activity. Furthermore, it provides methods for separating Zr on a yttrium target using this method. 89 Zr is used in radioimmunotherapy drugs to label drugs such as monoclonal antibodies.

[0007] To achieve the above objectives, the present invention provides the following technical solution.

[0008] A method for separating on a yttrium target 89 Zr's method includes the following steps:

[0009] (1) Containing 89 The Zr yttrium target was cooled, dissolved, and filtered.

[0010] (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected;

[0011] (3) The eluent obtained in step (2) is separated again by column chromatography or solution extraction. Then, it is washed and eluted with hydrochloric acid, and the second eluent is collected to obtain purified solution. 89 Zr.

[0012] As a further description of the technical solution of the present invention, in step (1), the cooling time is 20-30h.

[0013] As a further description of the technical solution of the present invention, in step (1), the cooling time is 24 hours.

[0014] As a further description of the technical solution of the present invention, in step (1), the solution for dissolving the yttrium target is a 0.1-1 mol / L HCl solution.

[0015] As a further description of the technical solution of the present invention, in step (1), the solution for dissolving the yttrium target is a 0.5 mol / L HCl solution.

[0016] As a further description of the technical solution of the present invention, in step (2), the extractant is an impregnation extractant, which includes at least one of tri-n-octylamine TOA, trioctylphosphine oxide TOPO, N,N-diisooctyldiglycolaminosinic acid D2EHDGAA or N,N-dioctyldiglycolaminosinic acid DODGAA.

[0017] As a further description of the technical solution of the present invention, in steps (2) and (3), the concentration of hydrochloric acid is 0.1-4 mol / L.

[0018] Preferably, in steps (2) and (3), the concentration of the hydrochloric acid is 3.5 mol / L.

[0019] As a further description of the technical solution of the present invention, in step (3), the column chromatography method uses an impregnated resin column; the impregnated resin column is of type XAD-16 and has an average particle size of 0.56-0.71 mm.

[0020] The resin impregnation method used in the separation process can be well automated, reducing the radiation dose to human personnel.

[0021] Another object of the present invention is to provide a method for separating on a yttrium target 89 The Zr method is used in the application of radioimmunotherapy drugs, specifically for the separation of Zr on a yttrium target. 89 Zr was obtained through concentration and enrichment. 89 Zr is used to prepare radioimmunotherapy drugs in vivo.

[0022] Based on the above technical solution, the technical effects achieved by the present invention are as follows:

[0023] (1) The present invention provides a method for separating on a yttrium target 89 The Zr method has the advantages of simple separation process, simple extractant preparation process, good separation efficiency, and high product abundance (purity). By simulating the separation conditions of yttrium zirconium with different gradient concentrations, the optimal conditions for yttrium zirconium separation under cold experimental conditions were successfully obtained. Under these conditions, the separated products... 89 The Zr purity is above 99%. Automated separation on resin-impregnated columns is used in hot chamber experiments, offering high tolerance for errors and minimizing the harmful effects of radioactivity on the human body.

[0024] (2) Separation on a yttrium target according to the present invention 89 Zr's method, which utilizes solvent extraction, can significantly shorten the separation process time and maximize the guarantee of... 89 Zr activity was increased, and workers' radiation exposure in the environment was reduced. This method was used to separate Zr on a yttrium target. 89 Zr is then used in the preparation of radioimmunotherapy drugs, such as for labeling monoclonal antibodies. Attached Figure Description

[0025] Figure 1 This is a graph showing the extraction performance test of the extractant at different hydrochloric acid concentrations in Example 2 of the present invention.

[0026] Figure 2 This is a graph showing the extraction performance test of the extractant at different extractant concentrations in Example 2 of the present invention.

[0027] Figure 3 This is a test graph showing the back-extraction effect of the extractant under different acid conditions in Example 2 of the present invention.

[0028] Figure 4 This is an extraction test diagram of the expanded yttrium zirconium concentration gradient extractant in Example 2 of the present invention.

[0029] Figure 5 This is the isotherm adsorption test diagram of the extractant in Example 2 of the present invention.

[0030] Figure 6 This is a Langmuir model diagram of Embodiment 2 of the present invention.

[0031] Figure 7 This is a Freundlich model diagram of Embodiment 2 of the present invention.

[0032] Figure 8 This is a kinetic adsorption test diagram of the extractant in Example 2 of the present invention.

[0033] Figure 9 This is a pseudo-first-order dynamic test diagram of Embodiment 2 of the present invention.

[0034] Figure 10 This is a pseudo-second-order dynamic test diagram of Embodiment 2 of the present invention. Detailed Implementation

[0035] To facilitate understanding of the present invention, a more comprehensive description will be given below in conjunction with the accompanying drawings and specific embodiments. The drawings illustrate preferred embodiments of the invention. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the invention.

[0036] Unless otherwise defined, 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. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0037] Example 1

[0038] This embodiment provides a method for separating on a yttrium target. 89 Zr's method includes the following steps:

[0039] (1) Containing 89The Zr yttrium target is cooled, dissolved, and filtered. The cooling time is 20-30 hours, and preferably 24 hours. The solution for dissolving the yttrium target is a 0.1-1 mol / L HCl solution, and preferably 0.5 mol / L.

[0040] (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected; wherein the extractant is an impregnation extractant, which includes at least one of tri-n-octylamine TOA, trioctylphosphine oxide TOPO, N,N-diisooctyldiglycolaminosinic acid D2EHDGAA or N,N-dioctyldiglycolaminosinic acid DODGAA; preferably, the extractant is D2EHDGAA extractant.

[0041] (3) Separation is performed by solution extraction or column chromatography.

[0042] A. Separate the eluent obtained in step (2) again, then wash and elute with hydrochloric acid, and collect the second eluent to obtain purified solution. 89 Zr. The concentration of hydrochloric acid is 0.1-4 mol / L, and after optimization, the concentration of hydrochloric acid is 3.5 mol / L.

[0043] B. When separating the eluent obtained in step (2) using column chromatography, the chromatographic column used is an impregnated resin column, the model of which is XAD-16, and the average particle size is 0.56-0.71 mm.

[0044] Example 2

[0045] This embodiment uses a solution extraction method to extract the solution. 89 Zr was separated from the yttrium target. The following describes the optimal conditions for the separation of yttrium zirconium using this solution extraction method.

[0046] 2.1 Extraction performance test under different hydrochloric acid concentrations

[0047] Separation on a yttrium target as provided in Example 1 89 The Zr method involves diluting the extractant D2EHDGAA to 10 mM / L, preparing a mixed metal ion aqueous solution with eight hydrochloric acid concentration gradients from 0.5 to 4 and a yttrium zirconium concentration of 10 mg / L. 4 mL of the diluted D2EHDGAA is then mixed with 4 mL of the yttrium zirconium metal ion solution and shaken at 200 rpm for 24 h at room temperature to ensure adsorption equilibrium. The adsorption effect of the extractant on zirconium is detected by inductively coupled plasma atomic emission spectrometry.

[0048] Figure 1 The graphs shown are test results of the extractant's extraction performance at different hydrochloric acid concentrations in this embodiment. Figure 1As shown, the extractant D2EHDGAA exhibits high selectivity for Zr separation under the condition of 0.5M (0.5mol / L) hydrochloric acid concentration, with an extraction rate of 93.55%.

[0049] 2.2 Extraction performance test at different extractant concentrations

[0050] Separation on a yttrium target as provided in Example 1 89 The Zr method involves preparing gradient solutions of extractant D2EHDGAA at concentrations of 10 mM / L, 15 mM / L, 20 mM / L, 25 mM / L, and 30 mM / L, and a mixed metal ion aqueous solution with a yttrium concentration of 5000 mg / L and a zirconium concentration of 5 mg / L.

[0051] Mix 4 mL of extractant of different concentrations with 4 mL of metal ion solution and shake for 24 h to ensure that adsorption reaches equilibrium.

[0052] Figure 2 The graphs shown are test results of the extractant extraction performance at different extractant concentrations in this embodiment. Figure 2 As shown, the extraction rate was 93.55% when the extractant concentration was 10 mM. With increasing extractant concentration, the extraction rate gradually increased and stabilized at around 99%. The extractant concentration is crucial to the extraction effect; generally, the higher the extractant concentration, the better the extraction effect. However, excessively high concentrations can affect the back-extraction effect. Therefore, the extraction and back-extraction effects were best when the extractant D2EHDGAA concentration was 15 mM / L.

[0053] 2.3 Test of back-extraction effect under different acid conditions

[0054] Following the method for separating 89Zr on a yttrium target provided in Example 1, hydrochloric acid concentrations of 1 M / L, 1.5 M / L, 2 M / L, 2.5 M / L, 3 M / L, 3.5 M / L, 4 M / L, 4.5 M / L, and 5 M / L were prepared; sulfuric acid concentrations of 0.1 M / L, 0.2 M / L, 0.4 M / L, 0.6 M / L, 0.8 M / L, 1 M / L, 2 M / L, 3 M / L, and 4 M / L were prepared; and nitric acid concentrations of 0.1 M / L, 0.2 M / L, 0.4 M / L, 0.6 M / L, 0.8 M / L, 1 M / L, 2 M / L, 3 M / L, and 4 M / L were prepared.

[0055] Under the experimental conditions in 2.1 and 2.2, prepare 200 ml of the adsorbed extract phase, and take 4 ml of each phase and mix with an equal volume of the prepared acid solution, shaking for at least 8 hours to ensure complete back-extraction.

[0056] Figure 3 The graphs shown are test results of the extractant back-extraction effect under different acid conditions in this embodiment. Figure 3As shown, under hydrochloric acid conditions, the maximum back-extraction efficiency of 55.89% was achieved at a concentration of 3.5M. Under nitric acid conditions, there was no back-extraction effect, while the back-extraction effect was the best under sulfuric acid conditions, with a back-extraction rate of 96.57% at a concentration of 0.4M, which can achieve the effect of single-stage high-efficiency back-extraction at low concentrations.

[0057] Depending on the different effects of zirconium, hydrochloric acid or sulfuric acid can be selectively used for back-extraction. The zirconium prepared in this embodiment ( 89 Zr is mainly used for radioimmunotherapy of tumors. It needs to be adapted to the human body environment and is back-extracted under the condition of 3.5M (3.5mol / L) hydrochloric acid.

[0058] 2.4 Expanding the Yttrium Zirconium Concentration Difference Adsorption Test

[0059] because 89 Zr is obtained by bombarding a yttrium target with a cyclotron beam. Therefore, the effect of a high concentration gradient of yttrium-zirconium on zirconium separation needs to be considered when separating yttrium-zirconium. Mixed metal ion solutions with yttrium-zirconium concentration ratios of 1:1, 1000:1, 10000:1, and 100000:1 were prepared respectively. The extractant D2EHDGAA was diluted to 15 mM / L. 4 mL of each of the mixed metal ion solution and the extractant solution were mixed and shaken for 24 h to ensure adsorption equilibrium was reached.

[0060] Figure 4 This is an expanded yttrium-zirconium concentration gradient extractant extraction test diagram from this embodiment, as shown below. Figure 4 As shown, complete separation of yttrium and zirconium can still be maintained even when the concentration difference of yttrium and zirconium is 10,000 times, and single-stage complete separation can be achieved in actual separation.

[0061] 2.5 Isothermal Adsorption Test

[0062] Zirconium metal ion aqueous solutions with concentrations of 5 mg / L, 10 mg / L, 20 mg / L, 40 mg / L, 60 mg / L, 80 mg / L, 100 mg / L, 150 mg / L, 200 mg / L, 250 mg / L, 300 mg / L, 350 mg / L, 400 mg / L, 450 mg / L, and 500 mg / L were prepared, with 0.5 M (0.5 mol / L) hydrochloric acid. Each solution was mixed with 4 mL of 15 mM / L D₂EHDGAA extractant and shaken thoroughly. Adsorption isotherms, Langmuir model data, and Freundlich model data were obtained.

[0063] Figure 5 This is the isotherm adsorption test diagram of the extractant in this embodiment. Figure 6 This is a Langmuir model diagram for this embodiment. Figure 7 This is a Freundlich model diagram for this embodiment. (See diagram below.) Figures 5-7As shown, the Freundlich model has a correlation coefficient greater than 0.99. The Freundlich model is an empirical model based on heterogeneous surface adsorption and usually exhibits an exponential trend.

[0064] The fact that 1 / n in the Freundlich model is less than 1 proves that the zirconium extraction process is monolayered and the adsorption is uniform. Based on the fitted data, the maximum extraction capacity of this extractant is 309.5 mg / g, which can effectively achieve the concentration and enrichment of zirconium, showing great promise for its application in later-stage in vivo radioimmunotherapy.

[0065] 2.6 Kinetic Adsorption Test

[0066] A zirconium metal ion solution with a concentration of 5 mg / L and a hydrochloric acid concentration of 0.5 M (0.5 mol / L) was prepared and mixed thoroughly with 15 mM / L D2EHDGAA extractant. The kinetic adsorption model was obtained by testing at 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 360 min, 480 min, 720 min, 1080 min, and 2440 min.

[0067] Figure 8 This is the kinetic adsorption test diagram of the extractant in this embodiment. Figure 9 This is a pseudo-first-order dynamic test diagram for this embodiment. Figure 10 This is a pseudo-second-order dynamic test diagram for this embodiment. (See diagram below.) Figures 8-10 As shown, the extraction process can be well fitted by a pseudo-second-order model, yielding R0. 2 =0.9999, indicating that the adsorption process is controlled by chemisorption. The extraction process rapidly reaches over 70% extraction efficiency within 15 minutes and reaches extraction equilibrium within 240 minutes. The entire extraction process is relatively fast and can achieve single-stage extraction. Because... 89 Zr activity decreases over time, and separation occurs. 89 The shorter the Zr extraction time, the smaller the impact on activity. The solvent extraction method used in this embodiment can shorten the separation process time to maximize the preservation of Zr activity. 89 Zr activity.

[0068] Furthermore, this embodiment employs solvent extraction for separation and purification. 89 Zr was obtained with a high abundance of over 99% purity. 89 Zr can reduce human radiation dose and improve product purity through simple automated process steps.

[0069] Example 3

[0070] Yttrium target 89 Zr automated separation method

[0071] (1) Transfer the solution to the impregnation resin. After the solution has completely passed through the resin, rinse the resin column with 3.5M (3.5mol / L) hydrochloric acid and collect the effluent. The impregnation resin is XAD-16 type with an average particle size of 0.56-0.71mm.

[0072] (2) Pass the above effluent through another resin column, elute the resin column with 3.5M (3.5mol / L) hydrochloric acid, collect the effluent, and obtain a high-abundance... 89 Zr.

[0073] Prepared using this method 89 The purity of Zr can reach over 99%.

[0074] Example 4

[0075] Separate from Example 2 or Example 3 89 Zr is used in the preparation of radiotherapy drugs, specifically through concentration and enrichment. 89 Zr is used to label radioactive immunotherapy drugs.

[0076] Monoclonal antibodies or peptides can be site-specifically conjugated using chelating agents such as DFO, DTPA, and DOTA, and then... 89 Zr can be radiolabeled to selectively obtain radioactive diagnostic / therapeutic molecular probes.

[0077] Alternatively, 89Zr-labeled pembrolizumab or atezolizumab can be used.

[0078] Example 5

[0079] This embodiment provides a method for separating on a yttrium target. 89 Zr's method includes the following steps:

[0080] (1) Containing 89 The Zr yttrium target was cooled, dissolved, and filtered. The cooling time was 24 hours. The solution used to dissolve the yttrium target was a 0.5 mol / L HCl solution.

[0081] (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected; wherein the extractant is D2EHDGAA impregnation extractant.

[0082] (3) The eluent obtained in step (2) was separated again by solution extraction, then washed and eluented with hydrochloric acid, and the second eluent was collected to obtain purified solution. 89 Zr. The concentration of hydrochloric acid is 3.5 mol / L.

[0083] Example 6

[0084] This embodiment provides a method for separating on a yttrium target. 89 Zr's method includes the following steps:

[0085] (1) Containing 89 The Zr yttrium target was cooled, dissolved, and filtered, with a cooling time of 20 h; the solution for dissolving the yttrium target was a 0.1 mol / L HCl solution.

[0086] (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected; wherein the extractant is tri-n-octylamine TOA.

[0087] (3) Separation was performed by column chromatography. The column used was an impregnated resin column, model XAD-16, with an average particle size of 0.56-0.71 mm.

[0088] Example 7

[0089] This embodiment provides a method for separating on a yttrium target. 89 Zr's method includes the following steps:

[0090] (1) Containing 89 The Zr yttrium target was cooled, dissolved, and filtered, with a cooling time of 20 h; the solution for dissolving the yttrium target was a 0.1 mol / L HCl solution.

[0091] (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected; wherein the extractant is tri-n-octylamine TOA.

[0092] (3) The eluent obtained in step (2) was separated again by solution extraction, then washed and eluented with hydrochloric acid, and the second eluent was collected to obtain purified solution. 89 Zr. The concentration of hydrochloric acid is 0.1 mol / L.

[0093] Example 8

[0094] This embodiment provides a method for separating on a yttrium target. 89 Zr's method includes the following steps:

[0095] (1) Containing 89 The Zr yttrium target was dissolved and filtered after cooling for 30 hours; the solution used to dissolve the yttrium target was a 1 mol / L HCl solution.

[0096] (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected; wherein the extractant is D2EHDGAA impregnation extractant.

[0097] (3) The eluent obtained in step (2) was separated again by solution extraction, then washed and eluented with hydrochloric acid, and the second eluent was collected to obtain purified solution. 89 Zr. The concentration of hydrochloric acid is 4.0 mol / L.

[0098] Example 9

[0099] 89 The source of Zr preparation. Due to 89 Y and 89 Zr differs from yttrium by only one proton in its structure, and the product can be obtained directly by applying a cyclotron to a yttrium target. 89 Zr, products are controlled by controlling the beam intensity. 89 Zr yield and activity are suitable for meeting growing clinical demands.

[0100] Preparation on a yttrium target 89 The specific implementation steps of Zr's method are as follows:

[0101] (1) The yttrium target cut to a fixed size is fixed on the target holder (Cu, Al or graphite material), the target is moved into the hot chamber of production, and the sample is moved to the working position by remote control robot to receive proton irradiation. The beam irradiation energy is between 10MeV and 20MeV, and a certain dose of irradiation is accumulated.

[0102] (2) Remove the target. Since the sample that has just been irradiated has been activated, the radioactivity of the target material is high. Therefore, the target material is collected in the hot chamber and cooled for 24 hours before being dissolved.

[0103] (3) Dissolve the yttrium target in 0.5 mol / L hydrochloric acid solution until it is completely dissolved, and then pass the dissolved solution through a microporous filter (0.25 μm) for later use.

[0104] The high abundance provided in this embodiment 89 The Zr preparation method is simple, has a reasonable separation process, and is time-efficient. 89 The beneficial effects of high Zr abundance.

[0105] The above description is merely an example and illustration of the structure of this invention, and while the description is specific and detailed, it should not be construed as limiting the scope of this invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this invention, and these obvious substitutions all fall within the protection scope of this invention.

Claims

1. A method for separating on a yttrium target 89 The Zr method is characterized by... Includes the following steps: (1) The yttrium target containing 89 Zr is dissolved and filtered after cooling the target. (2) The solution obtained in step (1) is separated using an extractant, washed and eluted with hydrochloric acid, and the first eluent is collected; (3) The eluate obtained in step (2) is separated again using a column chromatography method or a solution extraction method, then washed and eluted using hydrochloric acid, and a second eluate is collected, to obtain purified 89 Zr; In step (1), the solution for dissolving the yttrium target is a 0.1~1 mol / L HCl solution; In step (2), the extractant is an impregnation extractant, which includes at least one of tri-n-octylamine TOA, trioctylphosphine oxide TOPO, N,N-diisooctyl diethylene glycol ammonium acid D2EHDGAA or N,N-dioctyl diethylene glycol ammonium acid DODGAA; In steps (2) and (3), the concentration of the hydrochloric acid is 0.1-4 mol / L; In step (3), the column chromatography method uses an impregnated resin column, which is of type XAD-16 and has an average particle size of 0.56-0.71 mm.

2. Separation on a yttrium target according to claim 1 89 The Zr method is characterized by... In step (1), the cooling time is 20-30 hours.

3. The method of separating Zr from a yttrium target according to claim 2, wherein 89 The method of separating Zr from a yttrium target according to claim 1, wherein In step (1), the cooling time is 24 hours.

4. The method of separating Zr from a yttrium target according to claim 1, wherein 89 Zr is characterized by, In step (1), the solution for dissolving the yttrium target is a 0.5 mol / L HCl solution.

5. Separation on a yttrium target according to claim 1 89 The Zr method is characterized by... In steps (2) and (3), the concentration of the hydrochloric acid is 3.5 mol / L.

6. A method of separating 89 Zr on a yttrium target for use in radioimmunotherapy drugs, characterized in that, Separation on a yttrium target using any one of claims 1-5 89 Zr was obtained through concentration and enrichment. 89 Zr is used to prepare radioimmunotherapy drugs in vivo.

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