A process for preparing carrier-free lutetium-177

Abstract

The present invention provides a process for preparing carrier-free lutetium-177, belonging to the technical field of rare earth element extraction. The method includes: obtaining a solution to be treated containing lutetium element and ytterbium element and having a pH value less than or equal to 3; using an organic carboxylic acid solution as the mobile phase and a chromatographic packing material surface-modified with sulfonic acid groups as the stationary phase, loading the solution to be treated onto a separation column, and performing liquid chromatography separation to obtain a lutetium fraction and an ytterbium fraction; adjusting the pH value of the lutetium fraction to 1-3 to obtain a lutetium-containing acid solution; injecting the lutetium-containing acid solution into a lutetium desalting column, where lutetium ions are adsorbed in the lutetium desalting column, and then performing elution and dilute hydrochloric acid elution in sequence to obtain a concentrated lutetium chloride solution; the lutetium desalting column is a chromatographic column with an amino carboxylic acid-type chelating agent as the stationary phase. The present invention obtains high-concentration and high-purity lutetium chloride and ytterbium chloride through steps such as target dissolution of the target material, ytterbium-lutetium separation, lutetium desalting and concentration, and ytterbium desalting and recovery.

Description

Technical Field

[0001] The present invention belongs to the technical field of rare earth element extraction, and in particular relates to a carrier-free lutetium-177 preparation process, which can be used in nuclear medicine, for treatment and / or diagnosis purposes. Background Art

[0002] Lutetium-177 ( 177 Lu) is a low-energy β-nuclides with a half-life of 6.7 days. It has the advantages of a relatively long half-life, easy labeling of drug molecules such as antibodies and peptides, low β-ray energy, and short range in tissues. It is currently one of the most promising and market-dynamic integrated radioactive diagnostic and therapeutic nuclides.

[0003] at present, 177 Lu can be directly processed by nuclear reaction ( 176 Lu(n,γ) 177 Lu) or indirect method ( 176 Yb(n,γ) 177 Yb→ 177 Lu), the direct method ultimately produces a carrier 177 Lu; the indirect method obtains the carrier-free 177 There is a large amount of stable Lu-176 isotope in the carrier Lu-177 prepared by direct method, which makes 177 The specific activity of Lu is low, which is not conducive to the subsequent labeling of targeted drugs such as monoclonal antibodies and peptides, thereby affecting the diagnosis and treatment effect. 177 Lu has high specific activity and long half-life 177m Lu, impurity content is extremely low, and the absence of a carrier reduces the amount of precursor used for the labeled compound and increases the effective period of the nuclide labeling. However, the carrier-free 177 Lu is actually 176 Yb / 177 Lu mixture, the two need to be separated to obtain high purity, high specific activity carrier-free 177 Lu.

[0004] The existing preparation processes of unsupported lutetium-177 mainly include chromatography, electrochemistry and sodium amalgam. Among them, chromatography has a strong separation ability and can distinguish substances with slight differences. It has a large separation coefficient for heavy lanthanides lutetium and ytterbium with similar chemical properties. Therefore, it is the main method currently used in actual production. However, the coarse granular resins used are hundreds of microns and have a wide particle size distribution. They belong to medium and low pressure chromatography and have problems of low column efficiency and insufficient selectivity. The separation takes a long time. Invention patent applied by ITM Isotope Technology Munich AG: Production of high-purity unsupported lutetium-177 177 Lu compounds and methods without carrier addition 177The Lu compound (publication number: CN103718250A) uses four cation exchange chromatography columns in series for two-stage separation, and a single separation takes more than 220 minutes. The invention patent applied by Quzhou Research Institute of Zhejiang University: A method for separating and purifying carrier-free lutetium-177 (publication number: CN118668079A) uses extraction resin as the chromatographic packing material and also requires two separations to obtain lutetium with a purity of 80%, and a single separation takes 10 - 20 hours. In addition, after separating ytterbium and lutetium by ion exchange chromatography, post-treatment is required to remove the organic carboxylic acid introduced during the separation process to meet medical requirements. In the current technology, sulfonic acid resin is used as the post-treatment material, strong acid is used as the eluent, and then further evaporation treatment is carried out to evaporate the strong acid to dryness. Due to the strong corrosiveness of the strong acid, high requirements are imposed on the production plant and equipment, and this step also increases the production process and production time. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a preparation process for carrier-free lutetium-177, aiming to solve at least one technical problem in the background technology.

[0006] The present invention is implemented as follows:

[0007] A preparation process for carrier-free lutetium-177, which includes the following steps:

[0008] Obtain a target material to be separated containing lutetium element (including lutetium-177 isotope) and ytterbium element, and its pH value is less than or equal to 3.

[0009] Using an organic carboxylic acid solution as the mobile phase and a chromatographic packing material surface-modified with sulfonic acid groups as the stationary phase, load the target material to be separated onto the separation column and perform liquid chromatography separation to obtain a lutetium fraction and an ytterbium fraction.

[0010] Adjust the pH value of the lutetium fraction to 1 - 3 to obtain a lutetium-containing acid solution.

[0011] Inject the lutetium-containing acid solution into a lutetium desalting column, and lutetium ions are adsorbed in the lutetium desalting column, and then elution and dilute hydrochloric acid elution are carried out in sequence to obtain a concentrated lutetium chloride solution; the lutetium desalting column is a chromatographic column with an amino carboxylic acid type chelating adsorbent as the stationary phase.

[0012] Further, the specific operation of the liquid chromatography separation to obtain a lutetium fraction and an ytterbium fraction is as follows:

[0013] Use the mobile phase to flush the separation column to make the inside of the packing material reach an equilibrium state.

[0014] The injector injects the target material solution into the quantitative loop.

[0015] The target material to be separated in the quantitative loop enters the separation column driven by the mobile phase and starts to be separated. The lutetium fraction and ytterbium fraction flowing out of the separation column are respectively collected by detecting signals through an energy spectrum detector and / or an ultraviolet detector.

[0016] Furthermore, the preparation method of the target material to be separated is as follows: using the ytterbium-lutetium mixture obtained after reactor irradiation as the solid target material, adding one or more strong acid solutions of nitric acid, hydrochloric acid, sulfuric acid or hydrofluoric acid with a concentration of 0.5 mol / L to 12 mol / L to completely dissolve it, adjusting the pH to 0 - 3 to meet the chromatographic sample loading requirements, and preparing a mixture of ytterbium ions and lutetium ions as the target material to be separated.

[0017] Furthermore, the organic carboxylic acid is selected from at least one or more of lactic acid, α-hydroxyisobutyric acid, 2-hydroxy-2-methylbutyric acid, citric acid, ethylenediaminetetraacetic acid or their salts, and its concentration range is 0.01 mol / L to 0.6 mol / L.

[0018] Furthermore, the specific steps for obtaining the concentrated lutetium chloride solution include:

[0019] Pump deionized water into the lutetium desalting column to displace all the solution inside it;

[0020] Add hydrochloric acid or nitric acid with a concentration of 0.1 mol / L to 12 mol / L to the lutetium fraction to adjust its pH to 1 - 3, and mix the two evenly by gas stirring;

[0021] Provide power through gas pressure feeding or liquid pumping by a liquid delivery pump to transport the above-mentioned lutetium fraction to the lutetium desalting column, and the lutetium ions are adsorbed in the packing;

[0022] Pump deionized water into the lutetium desalting column for cleaning to remove the residual organic carboxylic acid;

[0023] Pump 0.05 - 0.5 mol / L dilute hydrochloric acid into the lutetium desalting column, and perform elution on the adsorbed lutetium ions for 2 - 5 BV (column volume) to obtain the concentrated lutetium chloride solution.

[0024] Furthermore, the method also includes ytterbium recovery, specifically: mixing the ytterbium fraction with hydrochloric acid and then entering the ytterbium desalting column, the ytterbium ions are adsorbed in the ytterbium desalting column, and then elution and high-concentration hydrochloric acid elution are carried out in sequence to obtain the concentrated lutetium chloride solution.

[0025] Furthermore, the method for ytterbium recovery specifically includes:

[0026] Load strong cation exchange resin as the adsorption packing into the ytterbium salt conversion column;

[0027] Pump deionized water into the ytterbium desalting column to displace all the preservation solution inside it;

[0028] Add 0.1 mol / L to 12 mol / L hydrochloric acid or nitric acid to the ytterbium fraction to adjust its pH to 1 - 3, and mix the two evenly by gas stirring;

[0029] Provide power through gas pressure feeding or liquid pumping by a liquid infusion pump to transport the above ytterbium fraction liquid into the ytterbium desalination column, and the ytterbium ions are adsorbed in the packing;

[0030] Pump deionized water into the ytterbium desalination column for cleaning to remove the residual organic carboxylic acid;

[0031] Pump 1 mol / L to 6 mol / L hydrochloric acid into the ytterbium desalination column to elute the adsorbed ytterbium ions to obtain a concentrated ytterbium chloride solution.

[0032] Furthermore, the particle size of the polymer or silica gel matrix chromatographic packing in the separation column is 2 mm - 3 mm, and the pore size is 2 Å - 100 Å; the specific surface area is 50 m 2 / g - 1000 m 2 / g.

[0033] The polymer matrix chromatographic packing modified with sulfonic acid groups can be obtained by sulfonating polystyrene polymer microspheres, and the sulfonic acid group content is 0.6 - 2.0 mmol / g;

[0034] The specific structure of the silica gel matrix chromatographic packing modified with sulfonic acid groups is shown as follows:

[0035] ;

[0036] Wherein: the gray solid spheres in the formula represent silica gel particles; n is an integer of 0 - 10 (preferably 0 - 3), R is a phenyl group or a 2 - hydroxyoxypropyl group, m is an integer of 0 - 10 (preferably 0 - 3); the bonding amount of sulfonic acid groups is 0.2 - 2.0 mmol / g.

[0037] Furthermore, the matrix of the amino carboxylic acid type chelating adsorbent in the lutetium desalination column is a styrene - glycidyl acrylate copolymer, its pore size is 20 Å - 300 Å; the particle size is 10 mm - 100 mm; the pore volume is 0.4 cm 3 / g - 1.5 cm 3 / g; the specific surface area is 50 m 2 / g - 300 m 2 / g; the raw materials for amino carboxylic acid modification are selected from at least one or two or more of nitrilotriacetic acid, ethylenediaminetetraacetic acid, and diethylenetriaminepentaacetic acid, and the amino carboxylic acid modification amount is 0.4 mmol / g - 1.2 mmol / g.

[0038] The present invention obtains high-concentration and high-purity lutetium chloride and / or ytterbium chloride through steps such as dissolving the target, separating ytterbium and lutetium, concentrating lutetium by desalting, and recovering ytterbium by desalting.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] 1. The present invention uses small-particle silica gel or polymer microspheres (2 - 30 mm) with a uniform particle size distribution as the separation medium, which has significant advantages such as high column efficiency, large separation selectivity, and fast separation speed. A single separation column can achieve the efficient preparation of trace lutetium-177, greatly shortening the separation time, reducing radioactive losses, and greatly simplifying the separation process, making it easy to scale up.

[0041] 2. The present invention uses an amino carboxylic acid chelating adsorbent for the post-treatment of lutetium desalting. After the filler achieves efficient adsorption of lutetium, dilute acid (0.05 - 0.5 M) can be used to elute lutetium, and the obtained highly concentrated LuCl3 solution can be directly used for radioactive labeling without evaporation post-treatment, further reducing the design requirements of the plant, simplifying the production process, and shortening the production time.

[0042] 3. Through four consecutive steps of optimized target dissolution, separation and purification, lutetium desalting and concentration, and ytterbium desalting and recovery, the whole process takes only 4 hours at the shortest. The purity of lutetium is greater than 98%, the yield is greater than 90%, and the recovery rate of the raw material ytterbium-176 is greater than 95%, showing obvious progress in production time compared with the existing process. Description of the Drawings

[0043] Figure 1 It is a schematic diagram of the process device of the present invention;

[0044] Illustration: 101 - target dissolution tank, 102 - sample tank; 201 - heat exchanger, 202 - six-way valve, 203 - separation column, 204 - first waste liquid tank, 205 - ultraviolet detector, 206 - energy spectrum detector, 207 - lutetium liquid collection tank, 208 - ytterbium liquid collection tank, 209 - multi-way valve, 210 - quantitative loop; 301 - lutetium desalting column, 302 - lutetium finished product tank, 303 - second waste liquid tank, 304 - energy spectrometer; 401 - ytterbium desalting column, 402 - ytterbium finished product tank, 403 - third waste liquid tank;

[0045] Figure 2 It is the chromatogram of ytterbium and lutetium separation obtained in Example 1;

[0046] Figure 3 It is the PXRD comparison chart of Yb2O3 recovered in Example 1 and purchased Yb2O3;

[0047] Figure 4 It is the chromatogram of ytterbium and lutetium separation obtained in Example 2;

[0048] Figure 5 The chromatogram of ytterbium and lutetium separation obtained in Example 3;

[0049] Figure 6 The chromatogram of ytterbium and lutetium separation obtained in Example 4;

[0050] Figure 7 The separation chromatogram obtained by doping commercially available radioactive lutetium-177 into a natural ytterbium and lutetium mixture;

[0051] Figure 8 The TLC detection chart for the radioactive labeling experiment of lutetium chloride. Detailed implementation manners

[0052] In order to make the objectives, technical solutions and advantages of the present invention more clear and understandable, the following further describes the present invention in detail with reference to embodiments. It should be understood that the specific implementation cases described herein are only used to explain the present invention and are not used to limit the present invention.

[0053] A preparation process of carrier-free lutetium-177, the method uses the device as shown in Figure 1 and includes steps S1 to S4.

[0054] The experiments carried out in the present invention are mainly cold experiments. Natural and stable lutetium oxide and ytterbium oxide are mixed to simulate the composition of the target material after reactor irradiation, and the mass ratio of the two is 4000:1.

[0055] S1. Using the ytterbium-lutetium mixture obtained after reactor irradiation as a solid target, adding one or more strong acid solutions of nitric acid, hydrochloric acid, sulfuric acid or hydrofluoric acid with a concentration of 0.5 mol / L to 12 mol / L to completely dissolve it, and then adjusting the pH to 0 to 3 to meet the requirements for chromatographic sample loading;

[0056] In specific implementation, the ytterbium-lutetium mixture is placed in the target dissolving tank 101 of the device. Inject an appropriate amount of one or more of nitric acid, hydrochloric acid, sulfuric acid or hydrofluoric acid into the tank through the inlet of the tank cover, turn on the heating device, heat at a certain temperature for a period of time, and stop heating after the solid target is completely dissolved; then transfer the dissolved target solution to be separated to the sample tank 102 through the liquid outlet at the bottom of the target dissolving tank 101 by air pressure. Subsequently, add alkaline or buffer reagent and other pH adjusting solutions to the target dissolving tank 101 in the same way and transfer them to the sample tank 102 to achieve the purpose of adjusting the pH and prepare the target liquid to be processed;

[0057] The advantage of separately transferring the target dissolving solution and the pH adjusting solution is that the target dissolving tank 101 can be rinsed to reduce sample loss.

[0058] S2. Using an organic carboxylic acid solution as the mobile phase, introduce the target liquid into the separation column to separate ytterbium ions and lutetium ions, and then separately collect the lutetium fraction and the ytterbium fraction;

[0059] In a specific implementation, the separation and purification system used in this step mainly includes a heat exchanger 201, a six-way valve 202, a separation column 203, a first waste liquid tank 204, an ultraviolet detector 205, an energy spectrum detector 206, a lutetium liquid collection tank 207, a ytterbium liquid collection tank 208, a multi-way valve 209, and a quantitative loop 210. At the same time, corresponding pipelines, control valves, pump bodies, etc. are also equipped. The heat exchanger 201 is used to adjust the temperature of the mobile phase. Two inlets of the six-way valve 202 are respectively connected to the outlet of the heat exchanger 201 and the outlet of the sample tank 102; two outlets of the six-way valve 202 are respectively connected to the upper end of the separation column 203 and the inlet of the first waste liquid tank 204; the six-way valve 202 also includes inlets and outlets connected to the quantitative loop 210 to form a cycle; after the liquid flows out of the separation column 203, it is divided into two flow paths, which are respectively connected to the ultraviolet detector 205 and the energy spectrum detector 206. The liquid after being detected by the ultraviolet detector 205 enters the first waste liquid tank 204. According to different detection signals, the liquid after being detected by the energy spectrum detector 206 flows into the lutetium liquid collection tank 207, the ytterbium liquid collection tank 208, and the first waste liquid tank 204 respectively.

[0060] Among them, a sulfonic acid group-containing polymer or silica matrix microspheres are provided in the separation column 203 as the stationary phase. Specifically, the surface of the polymer or silica is modified with sulfonic acid groups. The particle size of the polymer or silica matrix chromatographic packing is 2 mm - 30 mm, and the pore size is 2 Å ~ 100 Å; the specific surface area is 50 m 2 / g ~ 1000 m 2 / g.

[0061] The separation process of this step mainly includes two steps: system replacement and equilibration and ytterbium-lutetium separation;

[0062] Among them, system replacement and equilibration is carried out before the formal ytterbium-lutetium separation. The entire separation column 203 is flushed with an organic carboxylic acid as the mobile phase. The flow path is as follows: The mobile phase is pumped, heated by the heat exchanger 201, and then enters any separation column 203 through the six-way valve 202. After flowing out of the separation column 203, it is divided into two flow paths; a small branch (less than 3% of the total flow rate) passes through the reaction tube to react with the color reagent and then flows into the ultraviolet detector 205, and is discharged into the first waste liquid tank 204 after detection for waste liquid treatment; the main flow path (>97%) flows through the energy spectrum detector 206 and is discharged into the first waste liquid tank 204 through the multi-way valve 209; system replacement and equilibration is to make the inside of the packing reach an equilibrium state and the temperature reach the preset temperature by flushing the separation column with the mobile phase;

[0063] The flow path and the equilibration stage of the ytterbium-lutetium separation process are basically the same, except for an additional sample injection process. Specifically: Switch the six-way valve 202 to pump the target liquid in the sample tank 102 into the quantitative loop 210. Then switch the six-way valve 202 again, and the target liquid is carried into the separation column 203 by the mobile phase, and the separation process officially begins. The final destination of the main flow path depends on the signals of the ultraviolet detector 205 and the energy spectrum detector 206. According to the signals provided by these two detectors, control the switching of the multi-way valve 209. When the signal of lutetium is detected, it flows to the lutetium liquid collection tank 207; when the signal of ytterbium is detected, it flows to the ytterbium liquid collection tank 208, and in other cases, it flows to the first waste liquid tank 204. And there are several temperature sensors in the separation column 203 to continuously monitor the temperature of the ytterbium-lutetium separation system.

[0064] The eluent is a commonly used organic carboxylic acid in the art, which includes but is not limited to at least one of lactic acid, α-hydroxyisobutyric acid, 2-hydroxy-2-methylbutyric acid, citric acid, ethylenediaminetetraacetic acid or their salts, and its concentration range is 0.01 mol / L to 0.6 mol / L;

[0065] S3. After adjusting the pH of the lutetium fraction with hydrochloric acid or nitric acid, transfer the lutetium fraction liquid to the lutetium desalting column by air pressure loading or a liquid delivery pump. The lutetium ions are adsorbed in the lutetium desalting column, and then elution and dilute hydrochloric acid elution are carried out in sequence to obtain a concentrated lutetium chloride solution, which is carrier-free lutetium-177;

[0066] The separated lutetium fraction contains an organic carboxylic acid eluent and the lutetium fraction is very dilute, which does not meet the final use requirements. This step can not only remove the eluent and convert it into a lutetium chloride solution form suitable for medical use, but also concentrate the lutetium product.

[0067] In a specific implementation, the device used in this step mainly includes a lutetium desalting column 301, a lutetium finished product tank 302, a second waste liquid tank 303 and an energy spectrometer 304. The liquid flowing out of the lutetium desalting column 301 flows through the energy spectrometer 304 and then into the second waste liquid tank 303 and the lutetium finished product tank 302. At the same time, corresponding pipelines, control valves, pumps, etc. are also provided;

[0068] Among them, an amino carboxylic acid type chelating adsorbent is provided as the stationary phase in the lutetium desalting column 301.

[0069] The separation process of this step mainly includes steps such as system replacement, sample preparation, sample injection, elution and elution, specifically including:

[0070] (1) System replacement: Pump deionized water into the lutetium desalting column 301 to replace all the preservation solution inside it. It flows through the lutetium desalting column 301 and the energy spectrometer 304 and then into the second waste liquid tank 303;

[0071] (2)Sample preparation: Add hydrochloric acid or nitric acid with a concentration of 0.1 mol / L to 12 mol / L into the lutetium solution collection tank 207 to adjust the pH to between 1 and 3, and mix them evenly by gas stirring;

[0072] (3)Loading: Transfer the lutetium fraction solution in the lutetium solution collection tank 207 to the lutetium desalting column 301 by gas pressure feeding or liquid pumping by a liquid delivery pump, and the lutetium ions are adsorbed in the packing;

[0073] (4)Washing: Pump deionized water into the lutetium desalting column for cleaning to remove the residual organic carboxylic acid, and it is discharged into the second waste liquid tank 303 after flowing through the lutetium desalting column 301 and the energy spectrometer 304;

[0074] (5)Elution: Pump 0.05 - 0.5 mol / L dilute hydrochloric acid into the lutetium desalting column to elute the adsorbed lutetium ions to obtain a concentrated lutetium chloride solution, which is carrier-free lutetium-177, and it is discharged into the lutetium finished product tank 302 after flowing through the lutetium desalting column 301 and the energy spectrometer 304.

[0075] S4. Mix the ytterbium fraction with hydrochloric acid or nitric acid and then enter the ytterbium desalting column. The ytterbium ions are adsorbed in the ytterbium desalting column, and then washing and dilute hydrochloric acid elution are carried out in sequence to obtain a concentrated ytterbium chloride solution;

[0076] The separated ytterbium fraction contains an organic carboxylic acid eluent, which is not conducive to forming a precipitate. Therefore, through this step, the eluent can be removed and converted into a concentrated ytterbium chloride solution, which is convenient for subsequent further precipitation and calcination into ytterbium oxide. The obtained ytterbium oxide can be recycled as a target material raw material.

[0077] In a specific implementation, the device used in this step mainly includes an ytterbium desalting column 401, an ytterbium finished product tank 402, and a third waste liquid tank 403, and corresponding pipelines, control valves, pumps, etc. are also supporting;

[0078] Among them, a cation exchange resin is provided as a stationary phase inside the ytterbium desalting column 401.

[0079] The ytterbium recovery process can be divided into several steps such as system replacement, sample preparation, loading, washing, and elution, specifically as follows:

[0080] (1)System replacement: Pump deionized water into the ytterbium desalting column to replace all the preservation solutions inside it, and it is discharged into the third waste liquid tank 403 after flowing through the ytterbium desalting column 401;

[0081] (2)Sample preparation: Add hydrochloric acid or nitric acid with a concentration of 0.1 mol / L to 12 mol / L into the ytterbium solution collection tank 208 to adjust the pH to between 1 and 3, and mix the two evenly by gas stirring;

[0082] (3) Sample loading: The solution of the ytterbium fraction is transported into the ytterbium desalination column 401 by gas pressure feeding or liquid pumping by a liquid infusion pump, and ytterbium ions are adsorbed in the packing material.

[0083] (4) Elution: Deionized water is pumped into the ytterbium desalination column 401 for cleaning to remove residual organic carboxylic acids, and after flowing through the ytterbium desalination column 401, it is discharged into the third waste liquid tank 403.

[0084] (5) Elution: 1 mol / L to 8 mol / L hydrochloric acid is pumped into the ytterbium desalination column 401 to elute the adsorbed ytterbium ions, obtaining a concentrated ytterbium chloride solution, which is discharged into the ytterbium finished product tank 402 after flowing through the ytterbium desalination column 401.

[0085] Example 1

[0086] A preparation process of carrier-free lutetium-177, the method uses the device as Figure 1 shown, and it includes the following steps:

[0087] Step 1, Preparation of sulfonic acid group silica gel: 1 kg of dried silica gel microspheres (average particle size is 5 mm, pore size is 100 Å, specific surface area is 340 m 2 / g) are dispersed in 5 L of xylene, 0.2 kg of 2-(4-phenylsulfonyl chloride) ethyltrichlorosilane is added, heated to 110 °C, and reacted for 16 h. After the reaction, the temperature is lowered to below 50 °C, filtered by suction, washed successively with xylene and methanol, and dried by suction. Then, hydrolysis of the sulfonyl chloride group is carried out. The washed packing material is added to 5 L of 5 wt% sodium bicarbonate aqueous solution, stirred at room temperature for 16 h, filtered by suction, washed successively with water and methanol, and after drying by suction, it is placed in a vacuum drying oven, dried at a drying temperature of 80 °C for 12 h. The surface sulfonic acid group bonding density of the obtained sulfonic acid group silica gel packing material is about 0.4 mmol / g.

[0088] The silica gel microspheres with the following schematic structure are obtained:

[0089] ;

[0090] Step 2, Packing of high-performance separation chromatographic column: High-performance separation chromatographic column (inner diameter 50 mm, column length 250 mm), weigh 320 g of the sulfonic acid group silica gel packing material prepared in the above step 1, use methanol as the slurry solvent, uniformly disperse the packing material in the slurry solvent to obtain a slurry, then quickly pour the slurry into the chromatographic column tube, compress it with a column packing machine, the packing pressure is 10 Mpa, and when the slurry solvent is completely discharged from the column tube, the packing is completed, and its column efficiency is greater than 80,000 / meter, obtaining a separation column.

[0091] Step 3, dissolving the target: Using the stable ytterbium oxide-lutetium oxide composition to simulate the irradiated target material, weigh 100 mg of ytterbium oxide and 25 mg of lutetium oxide and mix them evenly. The mass ratio of the two is 4000:1. Add 8 mL of 2M nitric acid solution, heat to 80 °C to completely dissolve it, and then use 1 M ammonia water to adjust the pH to 0.5 to meet the requirements for chromatographic sample loading, obtaining the simulated dissolved solution of the target material to be separated.

[0092] Step 4, highly efficient separation of lutetium and ytterbium: Using an aqueous solution of 30 mmol / L α-hydroxyisobutyric acid (adjusted to pH 4.5 with 25-28 wt.% concentrated ammonia water) as the mobile phase, with a flow rate of 60 mL / min. First, rinse and elute the entire separation column with 2 BV of the mobile phase to bring the separation column to an equilibrium state; inject the dissolved solution of the target material into the quantitative loop through the injector, and then the mobile phase will carry the target liquid in the quantitative loop into the separation column. According to the signal provided by the ultraviolet detector, control the switching of the multi-way valve. When the signal of lutetium is detected, it flows to the lutetium solution collection tank, which is the lutetium fraction; when the signal of ytterbium is detected, it flows to the ytterbium solution collection tank, which is the ytterbium fraction. In other cases (when there is no ultraviolet signal of lutetium and ytterbium), it flows to the first waste liquid tank. The chromatogram is as Figure 2 shown, and this separation process only takes 1 hour.

[0093] Step 5, preparation of the stationary phase of the lutetium desalting column: Mix 30 mL of 1-bromododecane, 8 mL of glycidyl methacrylate, 30 mL of acrylamide, and 0.4 g of azobisisobutyronitrile evenly, and mix the oil phase with 1 L of the aqueous phase containing 4 g of polyvinyl alcohol and 19.5 g of sodium carbonate evenly. Stir at 800 rpm for 30 min, raise the temperature to 65 °C, and react for 4 h. The pore size of the obtained polymer microspheres is 120 Å; the particle size is 30 mm; the pore volume is 0.7 cm 3 / g; the specific surface area is 180 m 2 / g;

[0094] Add 10 g of the above polymer microspheres, 5 g of nitrilotriacetic acid, and 6 g of sodium bicarbonate to 150 mL of N,N-dimethylformamide, heat and stir at 90 °C for 24 hours, filter, and wash successively with methanol, 0.2 M hydrochloric acid solution, and water. The obtained solid is vacuum-dried in an oven at 60 °C for 16 hours to obtain a polymer material modified with nitrilotriacetic acid NTA. The modification amount of nitrilotriacetic acid NTA is 0.7 mmol / g;

[0095] Obtain polymer microspheres with the following schematic structure:

[0096] ;

[0097] The above polymer microspheres were packed into a PEEK chromatographic column with an inner diameter of 4.6 mm and a length of 100 mm as a lutetium desalination column for desalination and concentration of lutetium.

[0098] Step 6: Lutetium desalination and concentration: Before use, first replace all the preservation solution in the lutetium desalination column with 5 BV of deionized water; add 2 mol / L hydrochloric acid to the lutetium solution collection tank to adjust the pH of the lutetium fraction to 1, and mix the lutetium fraction and hydrochloric acid evenly by nitrogen bubbling and stirring to form a lutetium-containing acid solution; transfer the lutetium-containing acid solution to the lutetium desalination column by high-purity nitrogen pressure, and the lutetium ions are adsorbed on the amino carboxylic acid-type chelating adsorption packing; pump 20 BV of deionized water into the lutetium desalination column for cleaning to remove residual organic carboxylic acids; pump 0.1 mmol / L dilute hydrochloric acid (3 BV) into the lutetium desalination column to elute the adsorbed lutetium ions to obtain a concentrated lutetium chloride solution, which is carrier-free lutetium-177.

[0099] Step 7: Ytterbium desalination and concentration: The ytterbium desalination column (a PEEK chromatographic column with an inner diameter of 20 mm and a length of 150 mm) is packed with strong cation exchange resin (DOWEX® 50WX8 cation exchange resin). Before use, first replace all the preservation solution inside with 3 BV of deionized water; add 2 mol / L hydrochloric acid to the ytterbium solution collection tank to adjust the pH of the ytterbium fraction to 1, and mix the ytterbium fraction and hydrochloric acid evenly by nitrogen bubbling and stirring; transfer the ytterbium fraction solution to the ytterbium desalination column by high-purity nitrogen pressure, and the ytterbium ions are adsorbed on the packing; pump 3 BV of deionized water into the ytterbium desalination column for cleaning to remove residual organic carboxylic acids; pump 3 BV of 4 M hydrochloric acid into the ytterbium desalination column to elute the adsorbed ytterbium ions to obtain a concentrated ytterbium chloride hydrochloric acid solution.

[0100] Step 8: For the above concentrated ytterbium chloride hydrochloric acid solution, adjust the pH to 1.5 with 25 - 28 wt. % concentrated ammonia water, and then add 0.1 M oxalic acid solution with a molar amount 10 times that of ytterbium to obtain ytterbium oxalate precipitate, and then filter by suction to obtain ytterbium oxalate solid. Transfer the obtained precipitate to a crucible and calcine it in a muffle furnace at 850 °C for 2 hours to obtain 98.3 mg of Yb2O3 with a recovery rate of 98.3%. The powder X-ray diffraction pattern thereof is compared with Figure 3 as shown, no impurity peaks are observed, and it is confirmed that high-purity ytterbium oxide powder is recovered.

[0101] Example 2

[0102] On the basis of Example 1, the process and conditions are the same as those in Example 1, and the differences are as follows:

[0103] Step 1. Preparation of sulfonic acid group silica gel: 1 kg of dried silica gel microspheres (average particle size is 5 mm, pore size is 100 Å, specific surface area is 340 m 2 / g) are dispersed in 5 L of xylene, 1.5 L of 3-(2,3-epoxypropoxy)propyltrimethoxysilane is added, and the mixture is heated to 110 °C and reacted for 16 h. After the reaction, the temperature is cooled to below 50 °C, and then filtered. The product is washed successively with xylene and methanol, and then dried in a vacuum drying oven at 80 °C for 12 h to obtain epoxy silica gel. 1 kg of sodium bisulfite is mixed with 10 L of water, stirred until completely dissolved, and then the above epoxy silica gel is added. The reaction is carried out at 85 °C for 24 h, followed by filtration, and then washed successively with water and methanol. After drying, it is placed in a vacuum drying oven at 80 °C for 12 h. The surface sulfonic acid group bonding density of the obtained sulfonic acid group silica gel filler is about 0.4 mmol / g.

[0104] The silica gel microspheres with the following structure are obtained:

[0105] ;

[0106] Step 4. High-efficiency separation of ytterbium and lutetium: The obtained separation chromatogram is as Figure 4 shown.

[0107] Example 3

[0108] Based on Example 1, the process and conditions are the same as those in Example 1, except that:

[0109] In Step 3, dissolving the target: The composition of the target after simulating irradiation of stable ytterbium oxide-lutetium oxide is weighed. 200 mg of ytterbium oxide and 50 mg of lutetium oxide are mixed evenly, 16 mL of 1.5 M nitric acid solution is added, and the mixture is heated to 100 °C until completely dissolved. Then, 1 M ammonia water is used to adjust the pH to 0.2 to meet the requirements for chromatographic sample loading.

[0110] In the high-efficiency separation of ytterbium and lutetium in Step 4: The elution conditions in Step 4 are changed to an aqueous solution of 40 mmol / L 2-hydroxy-2-methylbutyric acid (adjusted to pH 4.4 with ammonia water) as the mobile phase, and the elution flow rate is 45 mL / min.

[0111] The lutetium-ytterbium separation chromatogram obtained in this example is as Figure 5 shown. As the processing amount increases to 200 mg, the ytterbium chromatographic peak tailing extends, and the separation time increases to 90 min.

[0112] Other steps and reaction conditions are the same as those in Example 1.

[0113] Example 4

[0114] Based on Example 1, the process and conditions are the same as those in Example 1, except that:

[0115] Adjust the 5 mm sulfonic acid group silica gel microspheres in the separation chromatographic column to sulfonic acid group polymer microspheres with an average particle size of 10 mm (particle size range 7 - 16 mm). The synthesis process (i.e., step 1) is as follows:

[0116] 24 g of polyethylene glycol mono - 4 - nonylphenyl ether (n≈5), 93.6 g of sodium chloride, 3.2 L of a 10% gelatin aqueous solution by mass concentration, and 8 L of pure water are placed in a 20 L three - necked flask, stirred at 600 rpm until dissolved clearly to obtain an aqueous phase; the oil phase containing 275.8 g of divinylbenzene, 200.2 g of n - heptane, 167.8 g of xylene, and 10.5 g of azobisisoheptanenitrile is mixed evenly, then mixed with the aqueous phase, the temperature is raised to 65 °C, and the reaction is carried out for 6 h. Wash with water and ethanol three times in sequence, and vacuum dry to obtain 700 mL of polymer microspheres. The pore diameter of this polymer microsphere is 50 - 100 Å; the particle size is 7 - 15 mm, the average particle size is 10 mm; the pore volume is 1.5 cm 3 / g; the specific surface area is 789 m 2 / g. Mix 500 mL of the above - mentioned polystyrene microspheres (average particle size 10 mm) evenly with 5.5 kg of 98% sulfuric acid by mass concentration, stir at 200 rpm, and react at 0 °C for 24 h. Wash the microspheres with water and ethanol to neutrality in sequence, and vacuum dry to obtain sulfonic acid group - modified polymer microspheres. The sulfonic acid group ion exchange capacity of this polymer microsphere is 1.62 mmol / g.

[0117] Dissolving the target in step 3: Simulate the composition of the irradiated target with stable ytterbium - lutetium oxide. Weigh 300 mg of ytterbium oxide and 75 mg of lutetium oxide and mix evenly, add 20 mL of 1.5 M nitric acid solution, heat to 120 °C to completely dissolve it, and then use 1 M ammonia water to adjust the pH = 0.2 to meet the chromatographic sample loading requirements.

[0118] Efficient separation of ytterbium and lutetium in step 4: Use an aqueous solution of 50 mmol / L α - hydroxyisobutyric acid (adjust the pH to 4.48 with 28 wt.% ammonia water) as the mobile phase, the flow rate is 50 mL / min. The lutetium - ytterbium separation chromatogram obtained in this example is as Figure 6 shown. When the processing amount is increased to 300 mg, due to the tailing of ytterbium, the separation time is further increased to 100 min.

[0119] Lutetium desalination and concentration in step 6: The aminocarboxylic complexing agent modified on the polymer surface is diethylenetriaminepentaacetic acid (DPTA), and the remaining reaction conditions are the same as those in Example 1; the modification amount of DTPA is 0.9 mmol / g, and the hydrochloric acid concentration in the elution step is increased to 0.4 M.

[0120] Example 5

[0121] On the basis of Example 1, the process and conditions are the same as in Example 1, except that:

[0122] In step 4, silica microspheres with an average particle size of 30 mm and a pore size of 100 Å were used; the specific surface area was 323 m 2 / g;

[0123] Efficient separation of ytterbium and lutetium in step 4: Replace the elution conditions in step 4 with 70 mmol / L lactic acid (pH adjusted to 4.7 with ammonia) as the mobile phase at a flow rate of 55 mL / min.

[0124] Step 6: Lutetium Desalting and Concentration: The aminocarboxylic acid complexing agent used to modify the polymer surface was replaced with ethylenediaminetetraacetic acid (EDTA). The remaining reaction conditions were the same as in Example 1. The modified amount of EDTA was 0.7 mmol / g. During the elution step, the hydrochloric acid concentration was increased to 0.5 M.

[0125] Example 6

[0126] Based on Example 1, the process and conditions are the same as Example 1, except that:

[0127] The particle size range of the sulfonic acid polymer microspheres in the separation column was adjusted to 20-40 mm, with an average particle size of 30 mm. The synthesis process (i.e., step 1) was as follows;

[0128] 80 g PVA-1788, 42 g sodium dodecylsulfonate, and 116.8 g sodium chloride were dispersed in 8 L of pure water and placed in a 20 L three-necked flask. Stirring at 400 rpm until clear resulted in an aqueous phase. The oil phase, containing 275.8 g divinylbenzene, 200.2 g n-heptane, 167.8 g xylene, and 10.5 g azobisisoheptonitrile, was mixed evenly and then mixed with the aqueous phase. The temperature was raised to 65°C and the reaction was allowed to proceed for 6 h. The product was washed three times with water and ethanol, respectively, and vacuum dried to obtain polymer microspheres. The pore size of the polymer microspheres was 50-100 Å; the particle size ranged from 20 to 40 mm, with an average particle size of 30 mm; and the pore volume was 1.43 cm 3 / g; specific surface area is 712 m 2 / g. 500 mL of the aforementioned polystyrene microspheres were mixed evenly with 5.5 kg of 98% concentrated sulfuric acid, stirred at 200 rpm, and reacted at 0°C for 24 h. The microspheres were washed with water and then ethanol until neutral, and then dried under vacuum to obtain sulfonic acid-modified polymer microspheres. The sulfonic acid group ion exchange capacity of these polymer microspheres was 1.58 mmol / g.

[0129] Efficient separation of ytterbium and lutetium in Step 4: Replace the elution conditions in Step 4 with an aqueous solution of 35 mmol / L citric acid (pH adjusted to 3.7 with ammonia water) as the mobile phase, and the elution flow rate is 55 mL / min.

[0130] Preparation of lutetium desalting adsorbent material in Step 5: Replace the aminocarboxylic complexing agent modified on the polymer surface with ethylenediaminetetraacetic acid (EDTA), and the remaining reaction conditions are the same as in Example 1. The modification amount of EDTA is 0.7 mmol / g. Increase the hydrochloric acid concentration to 0.5 M in the elution step.

[0131] Comparative Example 1

[0132] Based on Example 1, the process and conditions are the same as in Example 1, and the differences are as follows;

[0133] Replace the sulfonic acid groups modified on the silica gel surface in the separation chromatographic column with carboxylic acid groups. The specific synthesis process is as follows:

[0134] Disperse 1 kg of dried silica gel microspheres (average particle size is 5 mm, pore size is 100 Å, specific surface area is 340 m 2 / g) in 5 L of xylene, add 1.0 L of cyanopropyltrichlorosilane, heat to 110 °C, and react for 24 h. After the reaction, cool to below 50 °C, filter, wash successively with xylene and methanol, and after drying, put it into a vacuum drying oven at a drying temperature of 80 °C for 12 h to prepare cyanide-modified silica gel. Further disperse the cyanide-modified silica gel in 10 L of 0.1 mol / L hydrochloric acid water mixture, react at 90 °C for 24 h, filter, wash successively with water and methanol, and after drying, put it into a vacuum drying oven at a drying temperature of 80 °C for 12 h. The carboxyl group bonding density on the surface of the obtained carboxyl silica gel filler is about 0.5 mmol / g.

[0135] Obtain silica gel microspheres with the following structure:

[0136] ;

[0137] Efficient separation of ytterbium and lutetium in Step 4: Respectively use the elution conditions in Examples 1-6. It is found through experiments that when the carboxyl group is used as the surface modification group of the stationary phase, effective separation of lutetium and ytterbium cannot be achieved.

[0138] Comparative Example 2

[0139] Based on Example 1, the process and conditions are the same as in Example 1, and the differences are as follows;

[0140] Step 5: Preparation of lutetium desalting column: The lutetium desalting column (a PEEK chromatographic column with an inner diameter of 4.6 mm and a length of 100 mm) was filled with a strong cation exchange resin (DOWEX® 50WX8 cation exchange resin). After eluting with 2M hydrochloric acid for 10 BV, the recovery rate of lutetium ions was only 63%. Due to the large elution volume, the product concentration was relatively dilute, not meeting the usage requirements. After eluting with 4M hydrochloric acid for 4 BV, the recovery rate of lutetium ions was greater than 90%, but further evaporation was required to completely remove the 4M hydrochloric acid to meet the usage requirements for subsequent radioactive drug labeling. Due to the strong corrosiveness of hydrochloric acid, high requirements were placed on the plant equipment. Production equipment resistant to hydrochloric acid corrosion needed to be selected, and efficient ventilation facilities needed to be built. In addition, the evaporation step further increased the total processing time and radioactive losses.

[0141] The lutetium chloride and ytterbium chloride concentrates prepared in Examples 1 to 6 were subjected to elemental analysis tests using ICP-MS or ICP-OES, and the results are shown in Table 1 below.

[0142] Table 1 shows the elemental analysis tests for Examples 1 to 6

[0143]

[0144] From the data in Table 1, it can be seen that carrier-free lutetium-177 with high purity was prepared in Examples 1 to 6 of the present invention, and the yield was high. The organic carboxylic acids in the lutetium fraction were effectively removed through the lutetium desalting and concentration system. Dilute hydrochloric acid could be used to elute lutetium chloride, and the concentration of lutetium chloride was effectively increased, preparing carrier-free lutetium-177 that met medical requirements. In combination with the ytterbium desalting column, high-purity ytterbium chloride was recovered, achieving efficient recovery of the target material and further reducing production costs.

[0145] In Examples 1 to 3, stable ytterbium and lutetium solutions were used as simulated solutions for chromatographic separation and purification, and the obtained chromatograms are as Figures 3 to 5 shown, which only have UV signals.

[0146] Radioactive lutetium-177 purchased on the market was doped into a natural ytterbium and lutetium mixture, and the content ratio of radioactive lutetium-177 to stable lutetium was 1:17.7. According to the conditions of Example 1, the obtained separation pattern is as Figure 7 shown, which has both radioactive signals and UV signals. Radioactive isotopes and stable isotopes of the same element have the same chemical properties. Therefore, it is completely scientific and reasonable to use stable isotopes to replace radioactive isotopes for process development. Moreover, repeated separation experiments were carried out using samples doped with radioactive lutetium-177 multiple times, and no changes in the pattern were observed, indicating that the separation materials used in the process of the present invention have good radiation resistance. The obtained lutetium chloride (containing radioactive lutetium-177) solution was subjected to a radioactive labeling experiment, and the labeling molecule was DOTA. Finally, after iTLC detection, asFigure 8 As shown, the labeling rate of lutetium is 95.9%.

[0147] The above-described embodiments merely represent several implementation manners of the present invention. The description thereof is relatively specific and detailed, but it should not be construed as a limitation to the scope of the patent of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the appended claims.

Claims

1. A process for preparing carrier-free lutetium-177, characterized in that, The preparation process includes the following steps: The raw material to be separated and purified is a target solution to be separated containing lutetium and ytterbium elements and having a pH value less than or equal to 0.5; Chromatographic separation column is used for separation, with an organic carboxylic acid solution as the mobile phase and a chromatographic packing material surface-modified with sulfonic acid groups as the stationary phase. The target solution to be separated is loaded onto the separation column for liquid chromatography separation to obtain a lutetium fraction and an ytterbium fraction; Adjust the pH value of the lutetium fraction to 1 - 3 to obtain a lutetium-containing acid solution; Inject the lutetium-containing acid solution into a lutetium desalting column. The lutetium ions are adsorbed in the lutetium desalting column, and then elution and dilute hydrochloric acid elution are carried out in sequence to obtain a concentrated lutetium chloride solution of lutetium-177; the lutetium desalting column is a chromatographic column with an amino carboxylic acid-type chelating agent as the stationary phase; The matrix of the aminocarboxylic acid chelating adsorbent in the lutetium desalination column is a styrene-glycidyl acrylate copolymer, with a pore size of 20 Å to 300 Å; a particle size of 10 mm to 100 mm; a pore volume of 0.4 cm 3 / g to 1.5 cm 3 / g; the specific surface area is 50 m 2 / g to 300 m 2 / g; the raw materials for aminocarboxylic acid modification are selected from at least one or more of nitrilotriacetic acid, ethylenediaminetetraacetic acid, and diethylenetriaminepentaacetic acid, and the aminocarboxylic acid modification amount is 0.4 mmol / g to 1.2 mmol / g, The preparation method of the target solution to be separated is as follows: using the ytterbium-lutetium mixture obtained after reactor irradiation as a solid target, adding one or more strong acid solutions such as 0.5 mol / L - 12 mol / L nitric acid, hydrochloric acid, sulfuric acid or hydrofluoric acid to completely dissolve it, and adjusting the pH = 0 - 0.5 to meet the chromatographic sample loading requirements to prepare a mixture of ytterbium ions and lutetium ions as the target solution to be separated.

2. The carrier-free lutetium-177 preparation process according to claim 1, characterized in that, The specific operation of chromatographic separation to obtain a lutetium fraction and an ytterbium fraction is as follows: First, use the mobile phase to flush the separation column to make the inside of the packing material reach an equilibrium state; Inject the target solution to be separated into the quantitative loop through an injector; The target solution to be separated in the quantitative loop enters the separation column under the drive of the mobile phase and starts separation. The lutetium fraction and the ytterbium fraction flowing out of the separation column are collected by detecting signals through an energy spectrum detector and / or an ultraviolet detector respectively; The organic carboxylic acid is selected from at least one or more of lactic acid, α-hydroxyisobutyric acid, 2-hydroxy-2-methylbutyric acid, citric acid, and ethylenediaminetetraacetic acid, and the concentration range of the organic carboxylic acid solution is 0.01 mol / L - 0.6 mol / L.

3. The carrier-free lutetium-177 preparation process according to claim 1, wherein The preparation method of the chromatographic packing material surface-modified with sulfonic acid groups is as follows: (1) 1 kg of dried silica microspheres are dispersed in 5 L of xylene. The average particle size of the silica microspheres is 5 mm, the pore size is 100 Å, and the specific surface area is 340 m 2 / g. Then, 0.2 kg of 2-(4-phenylsulfonyl chloride)ethyltrichlorosilane is added, and the mixture is heated to 110 °C and reacted for 16 h. After the reaction, the temperature is cooled to below 50 °C, and filtration is carried out. The product is washed successively with xylene and methanol, and then dried by suction. Then, hydrolysis of the sulfonyl chloride group is carried out. The washed filler is added to 5 L of 5 wt% aqueous sodium bicarbonate solution and stirred at room temperature for 16 h. Filtration is carried out, and the product is washed successively with water and methanol. After drying by suction, it is placed in a vacuum drying oven at a drying temperature of 80 °C for 12 h. The surface sulfonic acid group bonding density of the obtained sulfonic acid group silica filler is 0.4 mmol / g, Or (2) 1 kg of dried silica microspheres are dispersed in 5 L of xylene. The average particle size of the silica microspheres is 5 mm, the pore diameter is 100 Å, and the specific surface area is 340 m 2 / g. Then, 1.5 L of 3-(2,3-epoxypropoxy)propyltrimethoxysilane is added, and the mixture is heated to 110 °C and reacted for 16 h. After the reaction, the temperature is cooled below 50 °C, and the mixture is filtered. It is washed successively with xylene and methanol, and then dried in a vacuum drying oven at a drying temperature of 80 °C for 12 h to obtain epoxy silica. 1 kg of sodium bisulfite is mixed with 10 L of water, and after stirring until completely dissolved, the above-mentioned epoxy silica is added, and the reaction is carried out at 85 °C for 24 h. It is filtered, washed successively with water and methanol, and then dried in a vacuum drying oven at a drying temperature of 80 °C for 12 h. The surface sulfonic acid group bonding density of the obtained sulfonic acid group silica filler is 0.4 mmol / g.

4. The process for preparing carrier-free lutetium-177 according to claim 1, wherein, The specific steps for obtaining the concentrated lutetium chloride solution include: Pump water into the lutetium desalting column to displace all the solution inside; Add 0.1 mol / L - 12 mol / L hydrochloric acid or nitric acid to the lutetium fraction to adjust its pH = 1 - 3, and mix the two evenly by gas stirring; Transport the above lutetium fraction to the lutetium desalting column by gas pressure feeding or liquid pumping by a liquid delivery pump, and the lutetium ions are adsorbed in the packing material; Pump water into the lutetium desalting column for cleaning to remove the residual organic carboxylic acid; Pump 0.05 mol / L - 0.5 mol / L dilute hydrochloric acid into the lutetium desalting column, and carry out 2 - 5 BV elution on the adsorbed lutetium ions to obtain a concentrated lutetium chloride solution.

5. According to the carrier-free lutetium-177 preparation process described in claim 1, characterized in that The preparation process further includes ytterbium recovery, specifically: mix the ytterbium fraction with 0.1 mol / L - 12 mol / L hydrochloric acid or nitric acid and then enter it into an ytterbium desalting column. The ytterbium ions are adsorbed in the ytterbium desalting column, and then elution and high-concentration hydrochloric acid elution are carried out in sequence to obtain a concentrated ytterbium chloride solution; The method for ytterbium recovery specifically includes: Load a strong cation exchange resin as an adsorption packing material into the ytterbium desalting column; Pump water into the ytterbium desalination column to completely replace the preservation solution inside it; Add 0.1 mol / L to 12 mol / L hydrochloric acid or nitric acid to the ytterbium fraction to adjust its pH to 1 - 3, and mix the two evenly by gas stirring; Transport the above ytterbium fraction liquid to the ytterbium desalination column by gas pressure feeding or liquid pumping by a liquid delivery pump, and the ytterbium ions are adsorbed in the packing; Pump deionized water into the ytterbium desalination column for cleaning to remove residual organic carboxylic acid; Pump 1 mol / L to 6 mol / L hydrochloric acid into the ytterbium desalination column to elute the adsorbed ytterbium ions to obtain a concentrated ytterbium chloride solution.

6. The carrier-free lutetium-177 preparation process according to claim 1 or 2, characterized in that, The particle size of the polymer or silica gel matrix microspheres in the separation column is 2 mm to 30 mm, the pore size is 2 Å to 100 Å, and the specific surface area is 50 m 2 / g to 1000 m 2 / g.

7. The process for preparing carrier - free lutetium - 177 according to claim 5, wherein: The strong cation exchange resin in the ytterbium desalination column is obtained by sulfonating polystyrene-based polymer microspheres, with the sulfonic acid group modification amount being 0.6 mmol / g to 4 mmol / g, its pore size being 20 Å to 300 Å; the particle size being 10 mm to 300 mm, and the specific surface area being 50 m 2 / g to 800 m 2 / g.

8. The carrier-free lutetium-177 preparation process according to claim 1, characterized in that: The preparation process comprises the following steps: The raw material to be separated and purified is a target solution to be separated containing lutetium element and ytterbium element and having a pH value less than or equal to 0.5; Use a chromatographic separation column for separation. Use an organic carboxylic acid solution as the mobile phase and a chromatographic packing modified with sulfonic acid groups as the stationary phase. Load the target solution to be separated onto the separation column and perform liquid chromatography separation to obtain a lutetium fraction and an ytterbium fraction; The process for obtaining the concentrated lutetium chloride solution is as follows: adjust the pH value of the lutetium fraction to 1 - 3 to obtain a lutetium - containing acid solution; Inject the lutetium - containing acid solution into the lutetium desalination column. The lutetium ions are adsorbed in the lutetium desalination column, and then perform elution and dilute hydrochloric acid elution in sequence to obtain a concentrated lutetium chloride solution of lutetium - 177; the lutetium desalination column is a chromatographic column with an amino - carboxylic acid - type chelating agent as the stationary phase; The process for obtaining the concentrated ytterbium chloride solution is as follows: mix the ytterbium fraction with 0.1 mol / L to 12 mol / L hydrochloric acid or nitric acid and then enter it into the ytterbium desalination column. The ytterbium ions are adsorbed in the ytterbium desalination column, and then perform elution and high - concentration hydrochloric acid elution in sequence to obtain a concentrated ytterbium chloride solution.

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