A method for separating 177 Lu 176 Yb mixtures 177 Lu

Abstract

This invention relates to a method from 177 Lu / 176 Separation of Yb mixture 177 Lu's method belongs to the field of medical radioisotope separation and purification technology, and solves one of the problems of existing methods requiring the addition of additional DGA resin for acid adjustment, resulting in high cost and complex processes. The method of this invention uses three TK resin columns connected in series for separation. 177 Lu, and the first TK resin column and the second TK resin column are respectively suitable for different acidities. 177 Lu / 176 Yb mixture liquid 177 Lu separation: the first and second TK resin columns serve as the separation components, while the third TK resin column only serves as the final separation component. 177 The method of this invention does not require additional DGA resin for acid adjustment, making the entire process simpler, reducing costs, and preventing radioactive gas leakage; furthermore, the method of this invention improves… 177 Lu recovery rate.

Description

Technical Field

[0001] This invention relates to the field of medical radioisotope separation and purification technology, and particularly to a method for separating and purifying medical radioisotopes. 177 Lu / 176 Separation of Yb mixture 177 Lu's method. Background Technology

[0002] In recent years, 177 Lu, as a medium-range radionuclide, has attracted widespread attention and research in the field of nuclear medicine for its use in targeted therapy. 177 Lu has become 131 One of the most promising treatments for radionuclides after I, although 177 Lu's therapeutic potential has only recently been fully recognized. In 2015, the EU announced that the German ITM Group... 177 The Lu product, which has received marketing authorization, is essentially a drug without a carrier, named EndolucinBeta. Meanwhile, multiple... 177 Lu-labeled peptide radiopharmaceuticals are also in clinical trials in Europe and the United States, for example 177 Lu-PSMA-617 177 Lu-NEOBOMBI and 177 Lu-PSMA-R2, etc. 177 There are two main methods for producing Lu: one is enrichment through irradiation. 176 Lu target, through [ 176 Lu(n, γ) → 177 Lu is produced through a "direct" pathway, and can also be enriched by irradiation. 176 Yb target[ 176 Yb(n, γ) 177 Yb→ 177 Lu] is produced through an "indirect" pathway. However, the "direct" production method can also produce metastable states. 177m Lu, a radionuclide with a half-life of 161 days, is considered a radionuclide impurity. The "indirect method" of production can yield carrier-free (NCA) with high specific activity. 177 Lu, and it will not produce 177m Lu. Although this method has low yields, (NCA) 177 Lu radionuclide therapy holds immense promise, hence this production route has been actively researched by foreign companies. The main challenge of this production route lies in separating trace amounts of ytterbium from a large ytterbium matrix. 177 Lu, and since both Yb and Lu are lanthanide elements with the same chemical properties, this further increases the difficulty of chemical separation.

[0003] Currently, the carrier-free methods reported in domestic and international literature and patents... 177The separation of Lu primarily employs lanthanide elution resins due to their excellent Yb / Lu separation capabilities and high adsorption capacity. Existing methods mainly utilize LN2 resin for elution, with DGA resin used to adjust the acidity of the feed solution. By combining these two resins, multi-stage separation and purification are achieved to ultimately obtain a product meeting medical standards. 177 Lu.

[0004] In existing separation processes, adjusting the acidity of the eluent typically requires the use of DGA resin or an evaporation and concentration step. Firstly, the additional introduction of DGA resin undoubtedly increases the complexity of the separation process, especially in multi-stage separation and purification where multiple LN2 and DGA resin columns are used in series. Furthermore, DGA resin is expensive, and its acid-adjusting function alone significantly increases separation costs. Whether the use of DGA resin can be reduced or eliminated in the ytterbium-lutetium separation process is crucial for its continued production. Secondly, adding an evaporation and concentration step not only increases the separation time but also potentially causes radioactive gas leaks. Summary of the Invention

[0005] In view of the above analysis, the present invention aims to provide a method from 177 Lu / 176 Separation of Yb mixture 177 Lu's method addresses one of the problems of existing separation processes that require the addition of additional DGA resin for acid adjustment, resulting in higher costs and more complex processes.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A kind of from 177 Lu / 176 Separation of Yb mixture 177 Lu's method includes the following steps:

[0008] (1) 177 Lu / 176 The Yb mixture is dissolved in acid to obtain a solution, which is then loaded onto a first TK resin column.

[0009] (2) Primary separation and purification: The first TK resin column was eluted with the first eluent to obtain the pre-separated product. 177 Lu eluent;

[0010] (3) The initial separation 177 Lu eluent was loaded onto the second TK resin column;

[0011] (4) Secondary separation and purification: The second TK resin column is eluted with the second eluent to obtain the separated and purified product.177 Lu eluent;

[0012] (5) Product acidity conversion: The separated and purified product... 177 Lu eluent was loaded onto the third TK resin column. First, the third TK resin was eluted with nitric acid solution, and then the third TK resin column was eluted with the third eluent to obtain... 177 Lu product solution.

[0013] Furthermore, in step (1), the first TK resin column is prepared by the following method: organophosphorus and organophosphonic acid are mixed in a mass ratio of 1-1.3, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it.

[0014] Furthermore, in step (1), the acid is nitric acid, and the concentration of nitric acid in the solution is 0.1-0.2M.

[0015] Furthermore, in step (2), the first eluent is a nitric acid solution with a concentration of 1.0-3.0M.

[0016] Furthermore, in step (3), the second TK resin column is prepared by the following method: organophosphorus and organophosphonic acid are mixed at a mass ratio of 1.4-1.6, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it.

[0017] Furthermore, the flow rate of the solution loaded onto the first TK resin column in step (1) is different from that in step (3) after initial separation. 177 The Lu eluent was loaded into the second TK resin column at the same flow rate.

[0018] Furthermore, in step (4), the second eluent is nitric acid with a concentration of 3.0-5.0M.

[0019] Furthermore, in step (2), the flow rate of the first eluent eluting the first TK resin column is the same as the flow rate of the second eluent eluting the second TK resin column in step (4).

[0020] Furthermore, in step (5), the third eluent is hydrochloric acid with a concentration of 0.01-0.1M.

[0021] Furthermore, in step (5), the third TK resin column is prepared by the following method: diethylene glycol amide and phosphine oxide are mixed at a mass ratio of 1.5-1, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it.

[0022] Furthermore, in step (5), 177 Lu product solutions meet medical standards.

[0023] Compared with the prior art, the present invention can achieve at least one of the following beneficial effects:

[0024] The method of this invention uses three TK resin columns connected in series for separation. 177 Lu, and the first TK resin column and the second TK resin column are respectively suitable for different acidities. 177 Lu / 176 Yb mixture liquid 177 Lu separation: the first and second TK resin columns serve as the separation components, while the third TK resin column only serves as the final separation component. 177 The method of this invention does not require additional DGA resin for acid adjustment, making the entire process simpler, reducing costs, and preventing radioactive gas leakage; furthermore, the method of this invention improves… 177 Lu has a high recovery rate and is economically viable.

[0025] In this invention, the above-described technical solutions can be combined with each other to achieve more preferred combinations. Other features and advantages of this invention will be set forth in the following description, and some advantages may become apparent from the description or be learned by practicing the invention. The objects and other advantages of this invention can be realized and obtained from what is particularly pointed out in the description and drawings. Attached Figure Description

[0026] The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. Throughout the drawings, the same reference numerals denote the same parts.

[0027] Figure 1 A method of the present invention from 177 Lu / 176 Separation of Yb mixture 177 Lu's process flow diagram;

[0028] Figure 2 As a comparative example 1 of the present invention 177 Lu / 176 Separation of Yb mixture 177 Lu's process flow diagram. Detailed Implementation

[0029] The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings, which constitute a part of the present invention and are used together with the embodiments of the present invention to illustrate the principles of the present invention, but are not intended to limit the scope of the present invention.

[0030] A specific embodiment of the present invention, such as Figure 1 As shown, a method from 177 Lu / 176 Separation of Yb mixture177 Lu's method includes the following steps:

[0031] (1) 177 Lu / 176 The Yb mixture is dissolved in acid to obtain a solution, which is then loaded onto a first TK resin column.

[0032] (2) Primary separation and purification: The first TK resin column was eluted with the first eluent to obtain the pre-separated product. 177 Lu eluent;

[0033] (3) The initial separation 177 Lu eluent was loaded onto the second TK resin column;

[0034] (4) Secondary separation and purification: The second TK resin column is eluted with the second eluent to obtain the separated and purified product. 177 Lu eluent;

[0035] (5) Product acidity conversion: The separated and purified product... 177 Lu eluent was loaded onto the third TK resin column. First, the third TK resin was eluted with nitric acid solution, and then the third TK resin column was eluted with the third eluent to obtain... 177 Lu product solution.

[0036] Compared with the prior art, the method of the present invention uses three TK resin columns connected in series for separation. 177 Lu, and the first TK resin column and the second TK resin column are respectively suitable for different acidities. 177 Lu / 176 Yb mixture liquid 177 Lu separation: the first and second TK resin columns serve as the separation components, while the third TK resin column only serves as the final separation component. 177 The method of this invention does not require additional DGA resin for acid adjustment, making the entire process simpler, reducing costs, and preventing radioactive gas leakage; furthermore, the method of this invention improves… 177 Lu has a high recovery rate and is economically viable.

[0037] In one specific embodiment, in step (1), the first TK resin column is prepared by the following method: organophosphorus and organophosphonic acid are mixed at a mass ratio of 1-1.3, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it.

[0038] In one specific embodiment, in step (1), the acid is nitric acid, and the concentration of nitric acid in the solution is 0.1-0.2M, for example, 0.1M, 0.12M, 0.14M, 0.16M, 0.18M, ​​or 0.2M.

[0039] It should be noted that in step (1), a certain concentration of nitric acid is first used to dissolve... 177 Lu / 176 After mixing the Yb, the nitric acid concentration was adjusted to 0.1-0.2M and then loaded onto the first TK resin column.

[0040] In one specific embodiment, in step (2), the first eluent is a nitric acid solution with a concentration of 1.0-3.0M. For example, the concentration of the nitric acid solution is 1.0M, 1.5M, 2.0M, 2.5M, or 3.0M.

[0041] It should be noted that in step (2), when the first TK resin column is eluted for the first time using the first eluent, most of the resin adsorbed on the resin column is first eluted. 176 Yb was eluted and separated, and then a second elution was performed on the first TK resin column to remove the adsorbed resin column. 177 Lu and the remainder 176 Yb was eluted and separated to obtain the pre-separated product. 177 Lu eluent.

[0042] In a preferred embodiment, in step (2), the volume ratio of the first eluent to the first elution and the second elution is 0.1-1, preferably 0.8.

[0043] In step (2), the total volume of the first eluent is 30-40 BV, of which, 176 The optimal elution volume for Yb is 15 BV, at which point it can achieve... 176 Yb and 177 Lu achieves optimal separation. 177 The optimal elution volume for Lu is 15-34 BV, which ensures... 177 Lu was fully eluted and recovered.

[0044] It should be noted that the volume of the first TK resin column is determined by... 177 Lu / 176 Yb mixture 176 The Yb content was determined. Specifically, the first TK resin column completely adsorbed... 176 After Yb, 20-99% of the adsorption redundancy should still be retained, preferably 94% of the adsorption redundancy.

[0045] The volume of the second TK resin column is determined by the volume of the column after initial separation in step (3). 177Lu eluent 176 The Yb content was determined, and the second TK resin column completely adsorbed the Yb. 176 After Yb, 20-99.9% of the adsorption redundancy should still be retained, preferably 99% of the adsorption redundancy.

[0046] Since the third TK resin column only serves to adjust the acidity and does not involve the separation of ytterbium and lutetium, theoretically, the amount of resin adsorbed should be approximately equal to the ytterbium and lutetium content in the feed solution. To reduce the amount of the third eluent, the volume of the third TK resin column can be selected according to actual needs; no specific limitation is made in this invention.

[0047] In one specific embodiment, in step (3), the second TK resin column is prepared by the following method: organophosphorus and organophosphonic acid are mixed at a mass ratio of 1.4-1.6, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it.

[0048] In one specific embodiment, the flow rate of the solution loaded onto the first TK resin column in step (1) is the same as that after initial separation in step (3). 177 The Lu eluent was loaded into the second TK resin column at the same flow rate of 3-6 mL / cm. 2 / min, for example, a flow rate of 3 mL / cm 2 / min, 3.5mL / cm 2 / min, 4.0mL / cm 2 / min, 4.6mL / cm 2 / min, 5.0mL / cm 2 / min, 5.5mL / cm 2 / min, 6.0mL / cm 2 / min.

[0049] In one specific embodiment, in step (4), the second eluent is nitric acid with a concentration of 3.0-5.0M, for example, with concentrations of 3.0M, 3.5M, 4.0M, 4.5M, and 5.0M.

[0050] In one specific embodiment, the flow rate of the first eluent eluting the first TK resin column in step (2) is the same as the flow rate of the second eluent eluting the second TK resin column in step (4), both being 0.6-1.2 mL / cm. 2 / min, for example, a flow rate of 0.6 mL / cm 2 / min, 0.7mL / cm 2 / min, 0.8mL / cm 2 / min, 0.9mL / cm 2 / min, 1.0mL / cm 2 / min, 1.1mL / cm 2 / min, 1.2mL / cm 2 / min.

[0051] It should be noted that in step (4), when eluting the second TK resin column with the second eluent, most of the adsorbed material on the second TK resin column is first removed. 176 Yb was eluted and separated for the first time; a second elution was then performed on the second TK resin column using a second eluent, removing the adsorbed material from the second TK resin column. 177 Lu and the remainder 176 Yb was eluted and separated; finally, the purified product was obtained. 177 Lu eluent.

[0052] In a preferred embodiment, the volume ratio of the second eluent in step (4) for the first elution and the second elution is 0.5-1.5, preferably 1.

[0053] In a preferred embodiment, in step (4), the total volume of the second eluent is 20-33 BV, wherein, 176 The optimal elution volume for Yb is 15 BV, at which point it can achieve... 176 Yb and 177 Lu achieves optimal separation. 177 The optimal elution volume for Lu is 15-30 BV, which ensures... 177 Lu was fully eluted and recovered.

[0054] In one specific embodiment, in step (5), the third eluent is hydrochloric acid with a concentration of 0.01-0.1M, for example, with concentrations of 0.01M, 0.02M, 0.03M, 0.04M, 0.05M, 0.06M, 0.07M, 0.08M, 0.09M, or 0.1M; and the concentration of the nitric acid solution is 0.01-0.1M.

[0055] In one specific embodiment, in step (5), the third TK resin column is prepared by the following method: diethylene glycol amide and phosphine oxide are mixed at a mass ratio of 1.5-1, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it.

[0056] It should be noted that in step (5), the separated and purified... 177 Lu eluent 177 Lu was almost entirely adsorbed onto the third TK resin column after elution. The third eluent was then used to elute the third TK resin column, yielding a product that met medical standards. 177 Lu product solution.

[0057] It should be noted that the components in this invention meet medical standards. 177 The pH value of the Lu product solution is 1.0-2.0. 177 Lu 3+ R f Value is 0.3-0.6, radiochemical purity is not less than 99%, Yb≤0.1μg·GBq -1 .

[0058] In step (5), the purified product is separated. 177 The flow rate of Lu eluent loaded onto the third TK resin column is the same as the flow rate of the second eluent eluting the second TK resin column in step (4).

[0059] In this invention, the first and second TK resin columns are prepared by mixing organophosphorus and organophosphonic acid in different proportions (organophosphorus:organophosphonic acid mass ratio of 1 to 1.5), and then adding an inert support. The organophosphorus contains long-chain alcohol groups, which act as free radical scavengers and increase the radiation stability of the resin. The inert support contains aromatic groups, which contribute to increasing the radiation stability of the resin.

[0060] For example, the organophosphonic acid may be di(2-ethylhexyl)phosphonic acid, and the organophosphonic acid may be 2-ethylhexylphosphonic acid mono(2-ethylhexyl) ester, but is not limited thereto.

[0061] The third TK resin column in this invention is prepared by mixing diethylene glycol amide and phosphine oxide in different proportions (diethylene glycol amide:phosphine oxide mass ratio of 1.5 to 1), and then adding an inert support. The diethylene glycol amide contains long-chain alcohol groups, and the organic phase is impregnated on the inert support containing aromatic groups to increase the stability against radiodegradation. The inert support contains aromatic groups, which helps to increase the radiation stability of the resin.

[0062] For example, the diethylene glycol amide may be N,N,N′,N′-tetraoctyl-3-oxoprandiamide, and the phosphine oxide may be trialkylphosphine oxide (TRPO), but is not limited thereto.

[0063] The inert support described in this invention is a common styrene-divinylphenyl macroporous adsorption resin with a particle size between 25-50 μm. The inert support contains aromatic groups, which also contributes to increasing the resin's radiation stability.

[0064] The technical solution of the present invention will be further explained below with reference to specific embodiments.

[0065] In the embodiments of the present invention, the first TK resin column is 1.5×30cm, 53mL; the second TK resin column is 1.5×16cm, 29mL; and the third TK resin column is 0.5×10cm, 2mL. The organophosphonic acid is di(2-ethylhexyl)phosphonic acid, and the organophosphonic acid is 2-ethylhexylphosphonic acid mono(2-ethylhexyl) ester.

[0066] The solutions used in the following examples are all the same, and each solution contains 100 mg 176 Yb and 0.5mg 177 Lu.

[0067] Example 1

[0068] like Figure 1 As shown, one embodiment of this method is from... 177 Lu / 176 Separation of Yb mixture 177 Lu's method includes the following steps:

[0069] (1) 177 Lu / 176 The Yb mixture is dissolved in nitric acid to obtain a solution with a nitric acid concentration of 0.1 M. The solution is loaded onto a first TK resin column at a flow rate of 8 mL / min, and the effluent from the column is collected in a waste liquid collection tank.

[0070] (2) Primary separation and purification: A 1.25M nitric acid solution was used as the first eluent to elute the first TK resin column at a flow rate of 1.6 mL / min. The eluent volume was 800 mL, which was collected in a dedicated collection tank. The first eluent was then used to further elute the adsorbed material on the first TK resin column. 177 Lu elution, with an eluent volume of 1000 mL, is the initial separation result. 177 Lu eluent;

[0071] (3) The initial separation 177 Lu eluent was loaded onto the second TK resin column at a flow rate of 1.6 mL / min;

[0072] (4) Secondary separation and purification: 4.0M nitric acid was used as the second eluent to elute the second TK resin column at a flow rate of 1.6 mL / min. The eluent was collected in the special collection tank in step (2), and the second eluent was used to further elute the adsorbed material on the second TK resin column. 177 Lu eluted, the eluent volume was 435 mL, which is the purified product. 177 Lu eluent;

[0073] (5) Product acidity conversion: The separated and purified product...177 Lu eluent was loaded onto the third TK resin column. First, the column was eluted with 6 mL of 0.1 M nitric acid at a flow rate of 8 mL / min. Then, the column was eluted with 0.05 M hydrochloric acid at a flow rate of 8 mL / min. 177 Lu elution, with an eluent volume of approximately 6 mL, meets medical standards. 177 Lu product liquid.

[0074] In this embodiment, the first TK resin column is selected as a TK212 resin column, the second TK resin column is selected as a TK211 resin column, and the third TK resin column is selected as a TK221 resin column.

[0075] The TK212 resin column was prepared as follows: Organic phosphine and organic phosphonic acid were mixed and dissolved in 200 ml of methanol at a mass ratio of 1.2, and then mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture was heated to 50 °C in a water bath and the methanol was removed by rotary evaporation for 1-2 h to obtain the TK212 resin column.

[0076] The TK211 resin column was prepared as follows: Organic phosphine and organic phosphonic acid were mixed and dissolved in 200 ml of methanol at a mass ratio of 1.5, and then mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture was heated to 50 °C in a water bath and the methanol was removed by rotary evaporation for 1-2 h to obtain the TK211 resin column.

[0077] The specific preparation of the TK221 resin column is as follows: Diethylene glycol amide and phosphine oxide are mixed at a mass ratio of 1.5 and dissolved in 200 mL of methanol. Then, it is mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture is heated to 50 °C in a water bath and the methanol is removed by rotary evaporation for 1-2 h to obtain the TK221 resin column.

[0078] In this embodiment, different feed solutions 176 Yb and 177 The Lu content is shown in Table 1.

[0079] Table 1

[0080]

[0081] Example 2

[0082] like Figure 1 As shown, one embodiment of this method is from... 177 Lu / 176 Separation of Yb mixture177 Lu's method includes the following steps:

[0083] (1) 177 Lu / 176 The Yb mixture is dissolved in nitric acid to obtain a solution with a nitric acid concentration of 0.1 M. The solution is loaded onto a first TK resin column at a flow rate of 8 mL / min, and the effluent from the column is collected in a waste liquid collection tank.

[0084] (2) Primary separation and purification: A 2M nitric acid solution was used as the first eluent to elute the first TK resin column at a flow rate of 1.6 mL / min. The eluent volume was 600 mL, which was collected in a dedicated collection tank. The first eluent was then used to further elute the adsorbed material on the first TK resin column. 177 Lu eluted, with an eluent volume of 800 mL, which is the initial separation result. 177 Lu eluent;

[0085] (3) The initial separation 177 Lu eluent was loaded onto the second TK resin column at a flow rate of 1.6 mL / min;

[0086] (4) Secondary separation and purification: 3.0M nitric acid was used as the second eluent to elute the second TK resin column at a flow rate of 1.6 mL / min. The eluent was collected in the special collection tank in step (2), and the second eluent was used to further elute the adsorbed material on the second TK resin column. 177 Lu eluted, the eluent volume was 480 mL, which is the purified product. 177 Lu eluent;

[0087] (5) Product acidity conversion: The separated and purified product... 177 Lu eluent was loaded onto the third TK resin column. First, the third TK resin column was eluted with 6 mL of 0.01 M nitric acid solution at a flow rate of 8 mL / min. Then, the column was eluted with 0.05 M hydrochloric acid at a flow rate of 8 mL / min. 177 Lu elution, with an eluent volume of approximately 6 mL, meets medical standards. 177 Lu product liquid.

[0088] The specific preparation methods of the first TK resin column, the second TK resin column, and the third TK resin column in this embodiment are as follows:

[0089] The first TK resin column was prepared as follows: organophosphorus and organophosphonic acid were mixed and dissolved in 200 ml of methanol at a mass ratio of 1, and then mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture was heated to 50 °C in a water bath and the methanol was removed by rotary evaporation for 1-2 h to obtain the TK212 resin column.

[0090] The second TK resin column was prepared as follows: organophosphorus and organophosphonic acid were mixed and dissolved in 200 ml of methanol at a mass ratio of 1.4, and then mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture was heated to 50 °C in a water bath and the methanol was removed by rotary evaporation for 1-2 h to obtain the TK211 resin column.

[0091] The specific preparation of the third TK resin column is as follows: Diethylene glycol amide and phosphine oxide are mixed at a mass ratio of 1 and dissolved in 200 mL of methanol. Then, it is mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture is heated to 50 °C in a water bath and the methanol is removed by rotary evaporation for 1-2 h to obtain the TK221 resin column.

[0092] In this embodiment, different feed solutions 176 Yb and 177 The Lu content is shown in Table 2.

[0093] Table 2

[0094]

[0095]

[0096] Example 3

[0097] like Figure 1 As shown, one embodiment of this method is from... 177 Lu / 176 Separation of Yb mixture 177 Lu's method includes the following steps:

[0098] (1) 177 Lu / 176 The Yb mixture is dissolved in nitric acid to obtain a solution with a nitric acid concentration of 0.1M. The solution is loaded onto a first TK resin column at a flow rate of 10 mL / min, and the effluent from the column is collected in a waste liquid collection tank.

[0099] (2) Primary separation and purification: A 1.25M nitric acid solution was used as the first eluent to elute the first TK resin column at a flow rate of 2.1 mL / min. The eluent volume was 800 mL, which was collected in a dedicated collection tank. The first eluent was then used to further elute the adsorbed material on the first TK resin column. 177 Lu elution, with an eluent volume of 1000 mL, is the initial separation result. 177 Lu eluent;

[0100] (3) The initial separation 177 Lu eluent was loaded onto the second TK resin column at a flow rate of 2.1 mL / min;

[0101] (4) Secondary separation and purification: 4.0M nitric acid was used as the second eluent to elute the second TK resin column at a flow rate of 2.1 mL / min. The eluent was collected in the special collection tank in step (2), and the second eluent was used to further elute the adsorbed material on the second TK resin column. 177 Lu eluted, the eluent volume was 435 mL, which is the purified product. 177 Lu eluent;

[0102] (5) Product acidity conversion: The separated and purified product... 177 Lu eluent was loaded onto the third TK resin column. First, the third TK resin column was eluted with 6 mL of 0.05 M nitric acid solution at a flow rate of 10 mL / min. Then, the column was eluted with 0.05 M hydrochloric acid at a flow rate of 10 mL / min. 177 Lu elution, with an eluent volume of approximately 6 mL, meets medical standards. 177 Lu product liquid.

[0103] The first TK resin column was prepared as follows: organophosphorus and organophosphonic acid were mixed and dissolved in 200 ml of methanol at a mass ratio of 1.3, and then mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture was heated to 50 °C in a water bath and the methanol was removed by rotary evaporation for 1-2 h to obtain the TK212 resin column.

[0104] The second TK resin column was prepared as follows: organophosphorus and organophosphonic acid were mixed and dissolved in 200 ml of methanol at a mass ratio of 1.6, and then mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture was heated to 50 °C in a water bath and the methanol was removed by rotary evaporation for 1-2 h to obtain the TK211 resin column.

[0105] The specific preparation of the third TK resin column is as follows: Diethylene glycol amide and phosphine oxide are mixed at a mass ratio of 1 and dissolved in 200 mL of methanol. Then, it is mixed with 20 g of styrene-divinylphenyl macroporous adsorption resin (particle size of 25-50 μm) inert support. The mixture is heated to 50 °C in a water bath and the methanol is removed by rotary evaporation for 1-2 h to obtain the TK221 resin column.

[0106] In this embodiment, different feed solutions 176 Yb and 177 The Lu content is shown in Table 3.

[0107] Table 3

[0108]

[0109] Comparative Example 1

[0110] like Figure 2 The diagram shows the process flow of this comparative example. The solution used in this comparative example is the same as that in Example 1. The volume of LN2 resin column 1 is 320 mL, and the volume of LN2 resin column 2 is 100 mL, both filled with LN2 resin produced by Triskem. The volume of DGA resin column 1 is 2 mL, and the volume of DGA resin column 2 is 2 mL, both filled with normal-DGA resin produced by Triskem. Eluent 1 is 1.8 M nitric acid, eluent 2 is 4 M nitric acid, and eluent 3 is 0.05 M hydrochloric acid.

[0111] This comparative example demonstrates a single-stage carrier-free lanthanide resin separation process. 177 Lu's method includes the following steps:

[0112] (a) The solution was loaded onto LN2 resin column 1 at a flow rate of 5 mL / min, and then eluent 1 was used at a flow rate of 1 mL / min to remove the adsorbed material from the LN2 resin column. 176 Yb was eluted, and the volume of eluent 1 was 7 BV, which was then collected.

[0113] (b) Next, eluent 2 was used at a flow rate of 5 mL / min to remove the adsorbed material from the LN2 resin column 1. 177 Lu elution, eluent 2 with a volume of 3 BV, is directly loaded onto DGA resin column 1;

[0114] (c) Use eluent 3 at a flow rate of 5 mL / min to remove the adsorbed DGA resin column 1 177 Lu elution, eluent 3, volume 9 BV, which is the initial separation result. 177 Lu eluent;

[0115] (d) After initial separation 177Lu eluent was continued to be loaded onto LN2 resin column 2, and then eluent 1 was used at a flow rate of 1 mL / min to remove the adsorbed material from the resin column. 176 Yb was eluted, and the eluent was collected at a volume of approximately 10 BV.

[0116] (e) Eluent 2 is then used at a flow rate of 5 mL / min to remove the adsorbed material from the LN2 resin column 2. 177 Lu elution, the volume of eluent 5 is 5 BV, and this eluent 5 is directly loaded onto DGA resin column 2;

[0117] (f) Use eluent 3 at a flow rate of 5 mL / min to remove the adsorbed material from the resin column. 177 Lu eluted, with an elution volume of approximately 9 BV, yielding the separated and purified product. 177 Lu product liquid.

[0118] In this comparative example, different feed solutions 176 Yb and 177 The Lu content is shown in Table 4.

[0119] Table 4

[0120]

[0121]

[0122] Comparative Example 2

[0123] This comparative example 177 The method for separating Lu is the same as in Example 1, except that the positions of the first TK resin column and the second TK resin column are swapped.

[0124] Comparative Example 3

[0125] This comparative example 177 The method for separating Lu is the same as in Example 1, except that the first eluent is a 4M nitric acid solution.

[0126] In this comparative example, different feed solutions 176 Yb and 177 The Lu content is shown in Table 5.

[0127] Table 5

[0128]

[0129] Comparative Example 4

[0130] This comparative example 177 The method for separating Lu is the same as in Example 1, except that the second eluent is a 0.05M nitric acid solution.

[0131] In this comparative example, different feed solutions 176 Yb and 177 The Lu content is shown in Table 6.

[0132] Table 6

[0133]

[0134] Comparative Example 5

[0135] This comparative example 177 The method for separating Lu is the same as in Example 1, except that the third eluent is 5M hydrochloric acid.

[0136] In this comparative example, different feed solutions 176 Yb and 177 The Lu content is shown in Table 7.

[0137] Table 7

[0138]

[0139] Experimental Example 1

[0140] Separation was performed using the methods of Examples 1-3 and Comparative Examples 1-5, respectively. 177 Lu, calculate the final product liquid 176 Yb and 177 The Lu content, separation effect, and resin dosage were compared, and the results are shown in Table 8.

[0141] Table 8

[0142]

[0143]

[0144] As can be seen from Table 3, the separation effects of Examples 1-3 are all better than those of Comparative Example 1, not only... 176 The removal rate of Yb is higher than that of control group 1, and 176 The Yb recovery rate was also higher than that of Comparative Example 1; in addition, the amount of resin used in Examples 1-3 was much smaller than that in Comparative Example 1, so the method of the present invention can reduce production costs and is more economical.

[0145] Compared with Example 1, Comparative Example 2 76 Yb removal rate slightly and 176 The Yb recovery rates were significantly lower than in Example 1. This is because the low acidity during the first separation process prevented the ytterbium and lutetium from being eluted, while the excessive acidity during the second separation process resulted in the complete elution of the ytterbium and lutetium, making separation impossible. Therefore, the resin column series sequence of this invention must be used to achieve better separation results.

[0146] Compared with Example 1, Comparative Examples 3-5 show that the first TK resin column, second TK resin column and third TK resin column of the present invention only have good separation effect when using the eluent concentration of the present invention.

[0147] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes 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.

Claims

1. A kind of from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, Includes the following steps: (1) 177 Lu / 176 The Yb mixture is dissolved in acid to obtain a solution, which is then loaded onto a first TK resin column. The first TK resin column is prepared by the following method: organophosphorus and organophosphonic acid are mixed at a mass ratio of 1-1.3, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it. (2) Primary separation and purification: The first TK resin column was eluted with the first eluent to obtain the pre-separated product. 177 Lu eluent; The first eluent is a nitric acid solution with a concentration of 1.0-3.0M; (3) The initial separation 177 Lu eluent was loaded onto the second TK resin column; The second TK resin column is prepared by the following method: organophosphorus and organophosphonic acid are mixed at a mass ratio of 1.4-1.6, dissolved in methanol, an inert support is added, and the mixture is heated and the methanol is evaporated to remove it. (4) Secondary separation and purification: The second TK resin column is eluted with the second eluent to obtain the separated and purified product. 177 Lu eluent; The second eluent is nitric acid with a concentration of 3.0-5.0M; (5) Product acidity conversion: The separated and purified product acidity conversion is carried out by converting the acidity of the product acidity into the acidity of the product acidity. 177 Lu eluent was loaded onto the third TK resin column. First, the third TK resin was eluted with nitric acid solution, and then the third TK resin column was eluted with the third eluent to obtain... 177 Lu product solution; The third TK resin column is prepared by the following method: diethylene glycol amide and phosphine oxide are mixed at a mass ratio of 1.5-1, dissolved in methanol, an inert carrier is added, and the mixture is heated and the methanol is evaporated to remove it. The third eluent is hydrochloric acid with a concentration of 0.01-0.1M.

2. A method according to claim 1 from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, In step (1), the acid is nitric acid, and the concentration of nitric acid in the solution is 0.1-0.2M.

3. A method according to claim 1 from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, In step (2), the first eluent is a nitric acid solution with a concentration of 1.5-2.5M.

4. A method according to claim 1 from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, The flow rate of the solution loaded onto the first TK resin column in step (1) is the same as that after the initial separation in step (3). 177 The Lu eluent was loaded into the second TK resin column at the same flow rate.

5. A method according to claim 1 from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, In step (4), the second eluent is nitric acid with a concentration of 3.5-4.5M.

6. A method according to claim 1 or 5 from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, In step (2), the flow rate of the first eluent eluting the first TK resin column is the same as the flow rate of the second eluent eluting the second TK resin column in step (4).

7. A method according to claim 1 from 177 Lu / 176 Separation of Yb mixture 177 Lu's method is characterized by, In step (5), the third eluent is hydrochloric acid with a concentration of 0.02-0.09M.

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