CN115810436A - Separation on yttrium target 89 Method and application of Zr - Google Patents

Abstract

The invention provides a method for separating ⁸⁹ Zr on a yttrium target, comprising the following steps: (1) dissolving and filtering the yttrium target containing ⁸⁹ Zr after cooling; (2) using an extractant to separate the solution obtained in step (1) , use hydrochloric acid to wash and analyze, and collect the first analysis solution; (3) adopt column chromatography or solution extraction method, separate the analysis solution obtained in step (2) again, then use hydrochloric acid to wash and analyze, and collect The second analysis solution was used to obtain purified ⁸⁹ Zr. The method separates ⁸⁹ Zr by using impregnated resin method and solvent extraction method; the impregnated resin method can be well automated in the process of use, reducing the artificial radiation dose; the solvent extraction method can shorten the separation time and ensure that ⁸⁹ Zr activity, reducing the radiation exposure of workers in the environment. The invention also provides the application of ⁸⁹ Zr separated on the yttrium target by the method in radioimmunotherapy medicine.

Description

A method and application of separating 89Zr on yttrium target

technical field

The invention relates to the technical field of radioactive isotope purification, in particular to a method and application for separating ⁸⁹ Zr on an yttrium target.

Background technique

The medical radionuclide Zr-89 (Zirconium-89, ⁸⁹ Zr) is often used to visualize and quantify the uptake of monoclonal antibodies (mAbs) because of its half-life of 3.3 days, making it ideal for PET imaging biomarkers to evaluate target protein expression and tumor targeting of monoclonal antibodies. Therefore, Zr-89 is an important research tool for many scientific institutions, research hospitals and pharmaceutical companies interested in protein imaging or therapy. For example, some researchers labeled pembrolizumab with ⁸⁹ Zr, and then performed positron emission tomography (PET) imaging studies to understand the optimal time point of PET scanning and the uptake of pembrolizumab.

It can be seen that in different stages of drug development, ⁸⁹ Zr radionuclide-based immunoPET imaging has always been an attractive imaging method, including lead compound screening, preclinical imaging, and mouse imaging. The model results are transformed into human body, etc.

⁸⁹ Zr is generally isolated from yttrium targets and then used in clinical applications, which needs to ensure that there is an appropriate amount of ⁸⁹ Zr to produce sufficient activity. Traditional methods for isotope separation include chemical separation, ion exchange chromatography, gas diffusion, laser and centrifugation. For example, the chemical separation method uses the different physical and chemical properties of the substances to be separated to separate. In the actual application process, the selectivity is usually not good, and it can only be used as a rough purification operation. It needs to be used in conjunction with other separation methods to obtain the target product. For ⁸⁹ Zr, which has decay properties, is not suitable. Moreover, the above-mentioned separation methods generally have problems such as long process flow, difficult elution of products, and excessively high elution acidity.

Due to the complexity of the ⁸⁹ Zr production process and its decay characteristics over time, it is difficult to separate high-abundance ⁸⁹ Zr that can be used in medicine from the yttrium target. Therefore, in order to separate and enrich ⁸⁹ Zr from the yttrium target, those skilled in the art need to develop a fast separation method with high separation performance and high abundance of the final product.

Contents of the invention

In order to solve the above-mentioned problems existing in the prior art, the present invention provides a method for separating ⁸⁹ Zr on the yttrium target, by using impregnation resin method and solvent extraction method to separate ⁸⁹ Zr; wherein, the impregnation resin method is used during It can realize automation well and reduce the artificial radiation dose; the solvent extraction method can greatly shorten the separation processing time, ensure the activity of ⁸⁹ Zr to the greatest extent, and also reduce the radiation exposure of workers in the environment. The invention also provides the application of the ⁸⁹ Zr separated on the yttrium target by the method in radioimmunotherapy drugs, for labeling drugs such as monoclonal antibodies.

In order to achieve the above object, the present invention provides the following technical solutions

A method for separating ⁸⁹ Zr on an yttrium target, comprising the following steps:

(1) Dissolving and filtering after cooling the yttrium target containing ⁸⁹ Zr;

(2) Using an extractant to separate the solution obtained in step (1), washing and analyzing with hydrochloric acid, and collecting the first analysis solution;

(3) Using column chromatography or solution extraction, separate the analytical solution obtained in step (2) again, then wash and analyze with hydrochloric acid, and collect the second analytical solution to obtain purified ⁸⁹ Zr.

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

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

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

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

As a further description of the technical solution of the present invention, in step (2), the extractant is an impregnation extractant, which includes tri-n-octylamine TOA, trioctylphosphine oxide TOPO, N,N-diisooctyldiglycol At least one of alkylamic acid D ₂ EHDGAA or N,N-dioctyl diglycol amic acid DODGAA.

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

Preferably, in step (2) and step (3), the concentration of the hydrochloric acid is 3.5mol/L.

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

In the separation process, the impregnation resin method can be well automated to reduce the artificial radiation dose.

Another object of the present invention is to provide a method for separating ⁸⁹ Zr on the yttrium target for application in radioimmunotherapy drugs. The method for separating ⁸⁹ Zr on the yttrium target can be concentrated and enriched to obtain ⁸⁹ Zr, and applied to Preparation of in vivo radioimmunotherapy drugs.

Based on above-mentioned technical scheme, the technical effect that the present invention obtains is:

(1) The method for separating ⁸⁹ Zr on the yttrium target provided by the present invention has the advantages of simple separation process operation, simple extraction agent preparation process, good separation efficiency, and high product abundance (purity). By simulating different gradient concentrations of yttrium Zirconium separation conditions, the best conditions for the separation of yttrium and zirconium under cold experimental conditions were successfully obtained, and the purity of ⁸⁹ Zr separated under this condition was above 99%. When conducting hot chamber experiments, automatic separation is carried out on the impregnated resin column, which not only has high fault tolerance, but also can minimize the damage of radioactivity to the human body.

(2) In the method for separating ⁸⁹ Zr on the yttrium target of the present invention, the solvent extraction method used can greatly shorten the time of separation and treatment, ensure the activity of ⁸⁹ Zr to the greatest extent, and also reduce the number of workers in the environment. radiation exposure. After ^{the 89} Zr is separated on the yttrium target by this method, it is applied to the preparation of radioimmunotherapy drugs, and is used to label drugs such as monoclonal antibodies.

Description of drawings

Fig. 1 is the test chart of the extraction performance of the extractant under different concentrations of hydrochloric acid in Example 2 of the present invention.

Fig. 2 is a test chart of the extraction performance of the extractant under different concentrations of the extractant in Example 2 of the present invention.

Fig. 3 is a test chart of stripping effect of extractant under different acid conditions in Example 2 of the present invention.

Fig. 4 is an extraction test chart of the expanded yttrium-zirconium concentration difference extractant in Example 2 of the present invention.

Fig. 5 is the isotherm adsorption test chart of the extractant in Example 2 of the present invention.

Fig. 6 is a Langmuir model diagram of Embodiment 2 of the present invention.

Fig. 7 is a Freundlich model diagram of Example 2 of the present invention.

Fig. 8 is the kinetic adsorption test chart of the extractant in Example 2 of the present invention.

Fig. 9 is a pseudo-first-order kinetics test diagram of Example 2 of the present invention.

Fig. 10 is a pseudo-second-order dynamics test diagram of Example 2 of the present invention.

Detailed ways

In order to facilitate the understanding of the present invention, the present invention will be described more fully below in conjunction with the accompanying drawings and specific embodiments. Preferred embodiments of the invention are shown in the accompanying drawings. However, the present invention can be embodied in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field of the invention. The terminology used herein in the description of the present invention is only for the purpose of describing specific embodiments, and is not intended to limit the present invention.

Example 1

This embodiment provides a method for separating ⁸⁹ Zr on an yttrium target, comprising the following steps:

(1) Dissolving and filtering the yttrium target containing ⁸⁹ Zr after cooling, wherein the cooling time is 20-30h, after optimization, the cooling time is 24h; the solution for dissolving the yttrium target is 0.1-1mol/L HCl solution, after optimization, The concentration of HCl solution is 0.5mol/L.

(2) Use the extractant to separate the solution obtained in step (1), use hydrochloric acid to wash and analyze, and collect the first analysis solution; wherein, the extractant is an impregnation extractant, which includes tri-n-octylamine TOA, trioctyl At least one of phosphine oxide TOPO, N, N-diisooctyl diglycol amic acid D ₂ EHDGAA or N, N-dioctyl diglycol amic acid DODGAA; preferably, the extractant is D ₂ EHDGAA extractant .

(3) Separation by solution extraction or column chromatography.

A. The analysis solution obtained in step (2) was separated again, then washed and analyzed with hydrochloric acid, and the second analysis solution was collected to obtain purified ⁸⁹ Zr. Wherein, the concentration of hydrochloric acid is 0.1-4mol/L, after optimization, the concentration of hydrochloric acid is 3.5mol/L.

B. When the analytical solution obtained in step (2) is separated by column chromatography, the chromatographic column used is an impregnated resin column. The type of this impregnated resin column is XAD-16 type, and the average particle diameter is 0.56-0.71mm .

Example 2

In this embodiment, a solution extraction method is used to separate ⁸⁹ Zr from the yttrium target. The following is to explore the optimal conditions for the separation of yttrium and zirconium under this solution extraction method.

2.1 Extraction performance test under different hydrochloric acid concentrations

According to the method for separating ⁸⁹ Zr on the yttrium target provided in Example 1, dilute the extractant D ₂ EHDGAA to 10mM/L, and prepare a mixture with a hydrochloric acid concentration gradient of 0.5-4, a total of eight points, and a yttrium-zirconium concentration of 10mg/L. Metal ion aqueous solution, mix diluted 4mL LD ₂ EHDGAA with 4mL yttrium-zirconium metal ion solution, shake in a shaker at room temperature 200rpm for 24h to ensure that the adsorption equilibrium is reached, and detect the adsorption effect of the extractant on zirconium by inductively coupled plasma atomic emission spectrometry .

Fig. 1 is the extraction performance test figure of the extractant under the different hydrochloric acid concentrations of the present embodiment, as shown in Fig. 1, the extractant D ₂ EHDGAA is under the condition of 0.5M (0.5mol/L) in the concentration of hydrochloric acid, shows to Zr High selective separation effect, the extraction rate is 93.55%.

2.2 Extraction performance test under different extractant concentrations

According to the method for separating ⁸⁹ Zr on the yttrium target provided in Example 1, the concentration of the extraction agent D ₂ EHDGAA was prepared respectively. Gradient solutions of 10mM/L, 15mM/L, 20mM/L, 25mM/L and 30mM/L An aqueous solution of mixed metal ions with a concentration of 5000mg/L and a zirconium concentration of 5mg/L.

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

Fig. 2 is the extractant extraction performance test chart under the different extractant concentrations of the present embodiment, as shown in Fig. 2, when extractant concentration is 10mM, extraction rate is 93.55%, along with the increase of extractant concentration, extraction rate gradually rises and gradually stabilizes at around 99%. The concentration of extractant is very important to the extraction effect. Generally speaking, the higher the concentration of extractant, the better the extraction effect, but too high concentration will affect the effect of stripping. Therefore, when the concentration of extractant D ₂ EHDGAA is 15mM/L, Extraction and stripping work best.

2.3 Test of stripping effect under different acid conditions

According to the method for separating 89Zr on the yttrium target provided in Example 1, the concentration of hydrochloric acid was prepared to be 1M/L, 1.5M/L, 2M/L, 2.5M/L, 3M/L, 3.5M/L, 4M/L , 4.5M/L and 5M/L, the concentration of sulfuric acid is 0.1M/L, 0.2M/L, 0.4M/L, 0.6M/L, 0.8M/L, 1M/L, 2M/L, 3M/L and 4M/L, the concentration of nitric acid is 0.1M/L, 0.2M/L, 0.4M/L, 0.6M/L, 0.8M/L, 1M/L, 2M/L, 3M/L and 4M/L.

Under the experimental conditions of 2.1 and 2.2, prepare 200ml of the extracted extraction phase after adsorption, and take 4mL respectively to mix and shake with the prepared acid solution in equal volume for more than 8 hours to ensure complete stripping.

Figure 3 is a test chart of the stripping effect of the extractant under different acid conditions in this embodiment. As shown in Figure 3, under the condition of hydrochloric acid, the maximum stripping efficiency is 55.89% when the concentration is 3.5M. Under the condition of nitric acid, there is no stripping effect, and the stripping effect is the best under the condition of sulfuric acid. When the concentration is 0.4M, the stripping rate reaches 96.57%, which can realize the effect of single-stage high-efficiency stripping at low concentration.

According to the different use effects of zirconium, hydrochloric acid or sulfuric acid can be selectively used for stripping. The zirconium ( ⁸⁹ Zr) prepared in this example is mainly used for radioimmunotherapy of tumors, and needs to be adapted to the human environment. The selected concentration is 3.5M (3.5mol /L) under hydrochloric acid conditions for stripping.

2.4 Expand the adsorption test of the concentration difference of yttrium and zirconium

Since ⁸⁹ Zr is obtained by bombarding the yttrium target with the cyclotron beam, it is necessary to consider the influence of the high concentration difference of yttrium and zirconium on the separation of zirconium when separating yttrium and zirconium. Prepare mixed metal ion solutions with yttrium-zirconium concentration ratios of 1:1, 1000:1, 10000:1 and 100000:1, dilute extractant D ₂ EHDGAA to 15mM/L, and take 4mL of mixed metal ion solution and extractant solution respectively Mix and shake for 24 hours to ensure that the adsorption equilibrium is reached.

Figure 4 is the extraction test chart of the expanded yttrium-zirconium concentration difference extractant of this embodiment, as shown in Figure 4, when the yttrium-zirconium concentration difference is 10,000 times, the complete separation of yttrium-zirconium can still be maintained, and single-stage separation can be realized in actual separation completely separable.

2.5 Isotherm adsorption test

Concentrations of 5mg/L, 10mg/L, 20mg/L, 40mg/L, 60mg/L, 80mg/L, 100mg/L, 150mg/L, 200mg/L, 250mg/L, 300mg/L, 350mg/L L, 400mg/L, 450mg/L and 500mg/L each 4mL zirconium metal ion aqueous solution, wherein the concentration of hydrochloric acid is 0.5M (0.5mol/L). Mix with 4mL15mM/L D ₂ EHDGAA extractant and shake fully. The adsorption isotherm, Langmuir model and Freundlich model were obtained.

Fig. 5 is the extraction agent isotherm adsorption test diagram of the present embodiment, Fig. 6 is the Langmuir model diagram of the present embodiment, and Fig. 7 is the Freundlich model diagram of the present embodiment. As shown in Figures 5 to 7, the fitting correlation coefficient of the Freundlich model is greater than 0.99, and the Freundlich model is an empirical model based on heterogeneous surface adsorption, which usually presents an exponential trend.

The 1/n of the Freundlich model is less than 1, which proves that the extraction process of zirconium is a single layer and the adsorption is uniform. According to the fitting data, the maximum extraction capacity of the extractant is 309.5mg/g, which can effectively realize the enrichment and utilization of zirconium, and the application of radioimmunotherapy in the later stage of the organism is very promising.

2.6 Kinetic adsorption test

A zirconium metal ion solution with a concentration of 5mg/L and a hydrochloric acid concentration of 0.5M (0.5mol/L) was prepared, mixed with 15mM/L D ₂ EHDGAA extractant and fully shaken. Tested at 15min, 30min, 45min, 60min, 90min, 120min, 180min, 240min, 360min, 480min, 720min, 1080min and 2440min to obtain the kinetic adsorption model.

Fig. 8 is the kinetic adsorption test chart of the extractant of this embodiment, Fig. 9 is the pseudo-first-order kinetic test chart of the present embodiment, and Fig. 10 is the pseudo-second-order kinetic test chart of the present embodiment. As shown in Figures 8 to 10, the extraction process can be well fitted by the pseudo-second-order model, and R ² =0.9999 is obtained, indicating that the adsorption process is controlled by chemical adsorption. The extraction process quickly reached more than 70% extraction efficiency in 15 minutes, and the extraction equilibrium was reached in 240 minutes. The entire extraction process is relatively fast, and single-stage extraction can be realized. Since the activity of ⁸⁹ Zr will decrease with time, the shorter the separation time of ⁸⁹ Zr, the smaller the effect on the activity. The solvent extraction method used in this example can shorten the time of separation and treatment, so as to ensure the activity of ⁸⁹ Zr to the greatest extent.

In addition, in this embodiment, a solvent extraction method was used to separate and purify ⁸⁹ Zr, and a high-abundance ⁸⁹ Zr with a purity of more than 99% was obtained. The artificial radiation dose can be reduced and the product purity can be improved through simple automatic process steps.

Example 3

Automatic Separation Method of ⁸⁹ Zr on Yttrium Target

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

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

The purity of ⁸⁹ Zr prepared by this method can reach more than 99%.

Example 4

^{The 89} Zr obtained from Example 2 or Example 3 is used in the preparation of radioimmunotherapy drugs, specifically, ⁸⁹ Zr obtained by concentration and enrichment is used for labeling radioimmunotherapy drugs.

Monoclonal antibodies or polypeptides can be site-specifically coupled with chelating agents such as DFO, DTPA, DOTA, etc., and radioactively labeled with ⁸⁹ Zr to selectively obtain radioactive diagnostic/therapeutic molecular probes.

89Zr can also be used to label pembrolizumab or atezolizumab.

Example 5

This embodiment provides a method for separating ⁸⁹ Zr on an yttrium target, comprising the following steps:

(1) Dissolve and filter the yttrium target containing ⁸⁹ Zr after cooling, wherein the cooling time is 24 hours; the solution for dissolving the yttrium target is 0.5 mol/L HCl solution.

(2) Using an extractant to separate the solution obtained in step (1), washing and analyzing with hydrochloric acid, and collecting the first analysis solution; wherein, the extractant is D ₂ EHDGAA impregnated extractant.

(3) Re-separate the analysis solution obtained in step (2) by solution extraction, then wash and analyze with hydrochloric acid, and collect the second analysis solution to obtain purified ⁸⁹ Zr. Wherein, the concentration of hydrochloric acid is 3.5mol/L.

Example 6

This embodiment provides a method for separating ⁸⁹ Zr on an yttrium target, comprising the following steps:

(1) Dissolve and filter the yttrium target containing ⁸⁹ Zr after cooling, wherein the cooling time is 20 h; the solution for dissolving the yttrium target is 0.1 mol/L HCl solution.

(2) Using an extractant to separate the solution obtained in step (1), washing and analyzing with hydrochloric acid, and collecting the first analysis solution; wherein, the extractant is tri-n-octylamine TOA.

(3) Column chromatography is used for separation, and the chromatographic column used is an impregnated resin column, the type of which is XAD-16, and the average particle diameter is 0.56-0.71mm.

Example 7

This embodiment provides a method for separating ⁸⁹ Zr on an yttrium target, comprising the following steps:

(1) Dissolve and filter the yttrium target containing ⁸⁹ Zr after cooling, wherein the cooling time is 20 h; the solution for dissolving the yttrium target is 0.1 mol/L HCl solution.

(2) Using an extractant to separate the solution obtained in step (1), washing and analyzing with hydrochloric acid, and collecting the first analysis solution; wherein, the extractant is tri-n-octylamine TOA.

(3) Re-separate the analysis solution obtained in step (2) by solution extraction, then wash and analyze with hydrochloric acid, and collect the second analysis solution to obtain purified ⁸⁹ Zr. Wherein, the concentration of hydrochloric acid is 0.1mol/L.

Example 8

This embodiment provides a method for separating ⁸⁹ Zr on an yttrium target, comprising the following steps:

(1) Dissolving and filtering the yttrium target containing ⁸⁹ Zr after cooling, wherein the cooling time is 30 h; the solution for dissolving the yttrium target is 1 mol/L HCl solution.

(2) Using an extractant to separate the solution obtained in step (1), washing and analyzing with hydrochloric acid, and collecting the first analysis solution; wherein, the extractant is D ₂ EHDGAA impregnated extractant.

(3) Re-separate the analysis solution obtained in step (2) by solution extraction, then wash and analyze with hydrochloric acid, and collect the second analysis solution to obtain purified ⁸⁹ Zr. Wherein, the concentration of hydrochloric acid is 4.0mol/L.

Example 9

The preparation source of ⁸⁹ Zr. Since there is only one proton difference in structure between ⁸⁹ Y and ⁸⁹ Zr, the product ⁸⁹ Zr can be obtained directly through the cyclotron action on the yttrium target, and the yield and activity of the product ⁸⁹ Zr can be controlled by controlling the intensity of the beam, which is suitable for meeting the growing clinical needs. Require.

The method for preparing ⁸⁹ Zr on the yttrium target, the specific implementation steps are as follows:

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

(2) Remove the target body. Since the sample that has just received irradiation has been activated, the radioactive activity of the target material is relatively high, so the target material is collected in a hot chamber and cooled for 24 hours before dissolving.

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

The high-abundance ⁸⁹ Zr preparation method provided in this example has the beneficial effects of simple method, reasonable separation process, short time consumption and high abundance of ⁸⁹ Zr.

The above content is only an example and description of the structure of the present invention, and the description is more specific and detailed, but should not be construed as limiting the patent scope of the present invention. It should be noted that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these obvious replacement forms all belong to the protection scope of the present invention.

Claims (10)

1. Separation on yttrium target ⁸⁹ The Zr method is characterized by comprising the following steps:

(1) Will contain ⁸⁹ Cooling the yttrium target of Zr, dissolving and filtering;

(2) Separating the solution obtained in the step (1) by using an extracting agent, washing and resolving by using hydrochloric acid, and collecting a first resolving solution;

(3) Separating the eluate obtained in step (2) again by column chromatography or solution extraction, washing with hydrochloric acid and eluting, and collecting the second eluate to obtain purified product ⁸⁹ Zr。

2. Separation on yttrium targets according to claim 1 ⁸⁹ Zr method, characterized in that in step (1) the cooling time is between 20 and 30h.

3. Separation on yttrium targets according to claim 2 ⁸⁹ Zr, characterized in that, in step (1), the cooling time is 24h.

4. Separation on yttrium targets according to claim 1 ⁸⁹ Zr characterized in that, in step (1), yttrium is dissolvedThe solution of the target is 0.1-1 mol/L HCl solution.

5. Separation on yttrium targets according to claim 1 ⁸⁹ The Zr method is characterized in that in the step (1), the solution for dissolving the yttrium target is 0.5mol/L HCl solution.

6. Separation on yttrium targets according to claim 1 ⁸⁹ Zr method, characterized in that, in step (2), the extractant is an impregnation extractant comprising tri-N-octylamine TOA, trioctylphosphine TOPO, N-diisooctyldiglycolic amic acid D ₂ At least one of EHDGAA or N, N-dioctyldiglycol amic acid DODGAA.

7. Separation on yttrium targets according to claim 1 ⁸⁹ Zr method, characterized in that, in step (2) and step (3), the concentration of hydrochloric acid is 0.1-4mol/L.

8. Separation on yttrium targets according to claim 7 ⁸⁹ Zr, characterized in that, in step (2) and step (3), the concentration of hydrochloric acid is 3.5mol/L.

9. Separation on yttrium targets according to claim 1 ⁸⁹ The method for Zr, characterized in that, in the step (3), the column chromatography adopts an impregnated resin column; the model of the impregnated resin column is XAD-16 type, and the average grain diameter is 0.56-0.71mm.

10. Separation on yttrium target ⁸⁹ Use of the method for Zr in radioimmunotherapy, characterized by the use of the yttrium target separation according to any of claims 1 to 9 ⁸⁹ Method for obtaining Zr by concentration and enrichment ⁸⁹ Zr and is applied to the preparation of the radioactive immunotherapy medicine in the organism.

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