Preparation method of lutetium trichloride solution

Abstract

The invention belongs to the technical field of preparation of medical radiopharmaceuticals, and particularly relates to a preparation method of a lutetium trichloride solution. A preparation method of a lutetium trichloride solution comprises the following steps: S.1, raw material loading: a lutetium-containing raw material is taken and conveyed to a transformation column to pass through the column, meanwhile, the pH value of the lutetium-containing raw material is adjusted to be within 3-10, and resin used by the transformation column is macroporous weak acid type cation exchange resin; s.2, washing with water to remove impurities: after the raw materials are conveyed, cleaning the transformation column by using sterilized injection water, and enabling the activity concentration of Lu-177 in the flowing-out solution to be lower than 1mCi / L; and S.3, chloridizing and leaching: leaching a lutetium trichloride aqueous solution from the impurity-removed transformation column by using hydrochloric acid. The weak acid type cation exchange resin adopted by the method has high adsorption capacity on Lu-177, organic impurities and impurity ions can be removed by pure water after loading lutetium, the leaching acidity is low, and the elution is fast. Meanwhile, the method does not generate a large amount of strong acid waste liquid and waste gas, follows the green principle, and improves the operation safety.

Description

Technical Field

[0001] This invention belongs to the field of medical radiopharmaceutical preparation technology, specifically relating to a method for preparing lutetium trichloride solution. Background Technology

[0002] Medical radionuclides are widely used in targeted radiotherapy due to their significant value in the early diagnosis and precision treatment of major diseases such as malignant tumors. In recent years, Lu-177 has gained attention due to its suitable β-ray diffusivity. - Particle energy (E β - With an activity of approximately 0.497 MeV, moderate gamma-ray emission (208 keV, 11%), and an ideal half-life of 6.65 days, Lu-177 has been successfully used to treat various solid tumors, including neuroendocrine tumors and prostate cancer. The mainstream production process for Lu-177 involves using high-abundance Yb-176 oxide as a target material. In a high-flux research reactor, neutron irradiation induces the Yb-176(n,γ)Yb-177→Lu-177 nuclear reaction, yielding carrier-free Lu-177. This indirect method produces a product with high specific activity, facilitating the labeling of peptides or small molecule ligands, making it an ideal source of radionuclides for personalized precision therapy.

[0003] However, the Lu-177 solution generated by this method contains a large amount of unreacted Yb-176, which, like Lu-177, belongs to the trivalent lanthanide series, has very similar ionic radii, and exhibits highly similar chemical properties, making separation and purification extremely difficult. Currently, the purification of Lu-177 typically employs ion-exchange chromatography with complexing agents such as α-hydroxyisobutyric acid, or extraction chromatography using phosphate esters or DGA-based extraction resins. While these methods can effectively separate Lu-177 from Yb-176, the purified lutetium is mainly present as an inorganic salt (lutetium nitrate, lutetium sulfate) or an organic complex solution. Since the final product required for clinical applications is an aqueous solution of lutetium trichloride, the purified product must undergo a transformation step to convert lutetium from other compound forms into an aqueous chloride solution.

[0004] The commonly used chlorination conversion technology involves first adsorbing lutetium ions onto a conversion column packed with macroporous or gel-type strongly acidic cation exchange resin, followed by rinsing with high-concentration hydrochloric acid to obtain a lutetium chloride solution. This method has the following prominent problems: First, the required hydrochloric acid concentration is generally above 3 mol / L, which is highly corrosive and can easily damage equipment and pose operational safety risks; second, the resulting lutetium chloride solution has a low concentration, requiring additional deacidification and concentration treatment to adjust the pH and activity concentration; third, the entire process is cumbersome, time-consuming, and generates large amounts of highly acidic waste liquid and waste gas, increasing the burden of radioactive waste treatment.

[0005] Therefore, there is an urgent need to develop a new chlorination conversion technology with milder acidity, higher conversion efficiency, and reduced post-processing steps, in order to shorten the production cycle, reduce acidic wastewater discharge, and improve the safety and industrial applicability of the Lu-177 preparation process. Summary of the Invention

[0006] To overcome the problems of easy equipment damage, high operation difficulty, low safety, low product concentration, cumbersome process, long time consumption, and easy generation of waste liquid and waste gas in the existing technology, the present invention provides a technical solution for the preparation of lutetium trichloride solution by first adsorbing lutetium ions through an online acidity adjustment process on a transformation column packed with macroporous weak acid cation exchange resin, and then rinsing with low concentration hydrochloric acid.

[0007] The present invention is implemented using the following technical solutions: In a first aspect, the present invention provides a method for preparing a lutetium trichloride solution, comprising the following steps: S.1 Raw material loading: Lutene-containing raw material is fed to the transformation column for column passage, while the pH value of the lutetene-containing raw material is adjusted to be within 3-10. The resin used in the transformation column is a macroporous weak acid cation exchange resin. S.2 Water washing to remove impurities: After the raw material is transported, the transformation column is washed with sterile water for injection. The activity concentration of Lu-177 in the outflow solution should be less than 1 mCi / L. S.3 Chlorination elution: Hydrochloric acid is used to elute the lutetium trichloride aqueous solution from the purified column.

[0008] Furthermore, the lutetium raw material mentioned in step S.1 includes an aqueous solution of lutetium nitrate, an aqueous solution of lutetium sulfate, or an aqueous solution of a complex.

[0009] Furthermore, the ligands corresponding to the complex in the aqueous solution include lactic acid, citric acid, ethylenediaminetetraacetic acid, or α-hydroxyisobutyric acid.

[0010] Furthermore, the acidity range of the lutetium-containing solution in step S.1 is 1 × 10⁻⁶. -5 -2 mol / L.

[0011] Furthermore, the lutetium content of the raw material in step S.1 is 1-100 Ci, calculated according to the total activity range.

[0012] Furthermore, the main active functional group of the macroporous weak acid cation exchange resin in step S.2 is a carboxyl group, and the ion exchange resin includes ammonium type, sodium type or potassium type.

[0013] Furthermore, the macroporous weak acid cation exchange resin described in step S.2 has a particle size of 75-800 μm.

[0014] Furthermore, the pH adjusting solution in step S.1 can be a single acid, a base, or a mixed solution, wherein the pH adjusting solution contains H... + or OH - The concentration range is 1-20 mol / L; the flow rate is 0.01-10 mL / min.

[0015] Furthermore, in step S.2, the flow rate of the sterile injection water is 1-20 mL / min, and the total volume is 50-1000 mL.

[0016] Furthermore, in step S.3, the concentration of hydrochloric acid used is 0.01-1 mol / L, the flow rate is 0.5-5 mL / min, and the total volume is 10-500 mL.

[0017] The present invention has the following beneficial effects: The weakly acidic cation exchange resin described in this invention has a high adsorption capacity for Lu-177. After loading lutetium, organic impurities and impurity ions can be removed with pure water, resulting in low elution acidity and rapid elution. High-purity lutetium trichloride (Lu-177) aqueous solution can be obtained using a single-column conversion process, avoiding the complex operation of multiple equipment processes in traditional conversion technologies.

[0018] This invention does not generate large amounts of strong acid waste liquid or waste gas, follows green principles, facilitates waste liquid treatment and recycling, and increases operational safety.

[0019] This invention is simple to operate and easy to learn, making it suitable for widespread application in production and experimentation. Attached Figure Description

[0020] Figure 1 This is a process flow diagram of the present invention.

[0021] Figure 2 The loading curve of lutetium in Example 1 is shown.

[0022] Figure 3 The lutetium loading curve is shown in Example 2.

[0023] Figure 4 The elution curve of lutetium in Example 3 is shown.

[0024] Figure 5 The elution curve of lutetium in Example 4 is shown. Detailed implementation method: The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that, unless otherwise specified, the following embodiments and features can be combined with each other. Unless otherwise specified, the methods used in the embodiments of the present invention are conventional methods, and the reagents used are commercially available.

[0025] Example 1 (e.g.) Figure 1 ): Step 1: Prepare the transformation column. Use a chromatography column with an inner diameter of 1 cm and pack 18 cm of weak acid cation exchange resin (ammonium type) with a particle size of 75-150 μm as the transformation column.

[0026] Step 2: A 1.5 mol / L nitric acid solution containing 40 μg lutetium (approximately 4 Ci) is loaded into the transformation column at a flow rate of 2 mL / min. A three-way valve is installed in the pre-column line, with one end connected to a pH adjustment solution. 10 mol / L ammonia solution is used as the pH adjustment solution at a flow rate of 0.3 mL / min. Simultaneously with the feedstock loading, the pH adjustment solution is delivered into the line via a liquid delivery device.

[0027] Step 3: Collect the leachate in segments and analyze the ion concentration using ICP-OES. The results are shown in [Figure number missing]. Figure 2 It can load 82% of lutetium.

[0028] Example 2: A 1.6 cm inner diameter chromatography column was used, packed with a 12 cm section of a weakly acidic cation exchange resin (ammonium form) with a particle size of 450-650 μm, as a transition column. A solution containing 800 μg lutetium (approximately 80 Ci) and an acidity of 1 x 10⁻⁶ was added. -4 A 0.24 mol / L lactate-sodium lactate mixed solution was loaded into the transformation column at a flow rate of 1 mL / min; 3 mol / L ammonia solution was used as the pH adjustment solution at a flow rate of 0.1 mL / min. The eluent was collected in fractions, and the ion concentration was analyzed by ICP-OES. The results are shown in [Figure number missing]. Figure 3 It can load 99% of the lutetium element.

[0029] Example 3: The lutetium-loaded transformation column was prepared according to the method in Example 2. Impurities were washed away by administering 300 mL of sterile water for injection at a rate of 4 mL / min. The lutetium product was then eluted with 0.6 mol / L hydrochloric acid. The eluent was collected in fractions, and the ion concentrations were analyzed by ICP-OES. The results are shown in [Figure 1]. Figure 4It can recover 87% of the lutetium element.

[0030] Example 4: The lutetium-loaded transformation column was prepared according to the method in Example 2. Impurities were washed away by administering 300 mL of sterile water for injection at a rate of 6 mL / min. The lutetium product was then eluted with 0.3 mol / L hydrochloric acid. The eluent was collected in fractions, and the ion concentrations were analyzed using ICP-OES. The results are shown in [Figure 1]. Figure 5 It can recover 93% of the lutetium element.

[0031] Example 5: A 1.6 cm inner diameter chromatography column was packed with 20 cm of weakly acidic cation exchange resin with a particle size of 500-700 μm as a transition column. A 1 mol / L nitric acid solution containing 1 Ci lutetium (Lu-177) was loaded into the transition column at a flow rate of 1.5 mL / min; 7 mol / L ammonia was used as the pH adjustment solution at a flow rate of 0.2 mL / min. After loading, 250 mL of sterile water for injection was injected at a flow rate of 6 mL / min to wash away impurities. The lutetium product was then eluted with 0.5 mol / L hydrochloric acid. The results of analysis of solutions with eluent volumes of 100-150 mL are shown in Table 1.

[0032] Table 1. Product parameters of lutetium trichloride (Lu-177) solution in Example 5 .

[0033] Example 6: A 1 cm inner diameter chromatography column was used, packed with a 10 cm thick weakly acidic cation exchange resin with a particle size of 75-150 μm, as a transition column. A column containing 10 Ci lutetium (Lu-177) and an acidity of 1 x 10⁻⁶ was prepared. -4 A 0.24 mol / L lactate-sodium lactate solution was loaded into the conversion column at a flow rate of 1 mL / min; 2 mol / L ammonia was used as the pH adjustment solution at a flow rate of 0.1 mL / min. After loading, 350 mL of sterile water for injection was injected at a flow rate of 6 mL / min to wash away impurities. Then, the lutetium product was eluted with 0.3 mol / L hydrochloric acid. The results of the analysis of solutions with eluent volumes of 110–170 mL are shown in Table 2.

[0034] Table 2. Product parameters of lutetium trichloride (Lu-177) solution in Example 6 .

Claims

1. A method for preparing a lutetium trichloride solution, characterized in that, Includes the following steps: S.1 Raw material loading: Lutene-containing raw material is fed to the transformation column for column passage, while the pH value of the lutetene-containing raw material is adjusted to be within 3-10. The resin used in the transformation column is a macroporous weak acid cation exchange resin. S.2 Water washing to remove impurities: After the raw material is transported, the transformation column is washed with sterile water for injection. The activity concentration of Lu-177 in the outflow solution should be less than 1 mCi / L. S.3 Chlorination elution: Hydrochloric acid is used to elute the lutetium trichloride aqueous solution from the purified column.

2. The method for preparing a lutetium trichloride solution as described in claim 1, characterized in that, The lutetium raw material mentioned in step S.1 includes an aqueous solution of lutetium nitrate, an aqueous solution of lutetium sulfate, or an aqueous solution of a complex.

3. The method for preparing a lutetium trichloride solution as described in claim 2, characterized in that, The ligands corresponding to the complex in the aqueous solution include lactic acid, citric acid, ethylenediaminetetraacetic acid, or α-hydroxyisobutyric acid.

4. A method for preparing a lutetium trichloride solution as described in claim 2 or 3, characterized in that, The acidity range of the lutetium-containing solution in step S.1 is 1 × 10⁻⁶. -5 -2 mol / L.

5. The method for preparing a lutetium trichloride solution as described in claim 1, characterized in that, The lutetium content of the raw material in step S.1 is 1-100 Ci, calculated based on the total activity range.

6. The method for preparing a lutetium trichloride solution as described in claim 1, characterized in that, The active functional group of the macroporous weak acid cation exchange resin in step S.1 is a carboxyl group, and the ion exchange resin includes ammonium type, sodium type or potassium type.

7. The method for preparing a lutetium trichloride solution as described in claim 6, characterized in that, The macroporous weak acid cation exchange resin described in step S.1 has a particle size of 75-800 μm.

8. The method for preparing a lutetium trichloride solution as described in claim 1, characterized in that, Step S.1 The pH adjusting solution can be a single acid, a base, or a mixed solution, wherein the pH adjusting solution contains H + or OH - The concentration range is 1-20 mol / L; the flow rate is 0.01-10 mL / min.

9. The method for preparing a lutetium trichloride solution as described in claim 1, characterized in that, The sterile injection water used in step S.2 has a flow rate of 1-20 mL / min and a total volume of 50-1000 mL.

10. The method for preparing a lutetium trichloride solution as described in claim 1, characterized in that, In step S.3, the concentration of hydrochloric acid used is 0.01-1 mol / L, the flow rate is 0.5-5 mL / min, and the total volume is 10-500 mL.

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