A method and apparatus for separating bismuth from actinium

Abstract

The application discloses a method for separating bismuth from actinium, which comprises the following steps: passing a hydrochloric acid or nitric acid solution containing actinium through a cation exchange column, and eluting the cation exchange column with first hydrochloric acid to obtain an eluate containing bismuth (Bi); passing the eluate containing Bi through a TK201 resin column to obtain Bi adsorbed on the TK201 resin column; and eluting the Bi adsorbed on the TK201 resin column with second hydrochloric acid or nitric acid to obtain a Bi eluate. The application uses TK201 resin as a purifying material of Bi for the first time, the TK201 resin is synthesized based on a tertiary amine and doped with a small amount of long-chain alcohol, has specific adsorption on Bi under the condition of a certain concentration of hydrochloric acid, and has no adsorption capacity on Ac and Fr, so that the content of Ac in Bi is greatly reduced.

Description

Technical Field

[0001] This invention relates to the field of radionuclide targeted therapy technology, and in particular to a method and apparatus for separating bismuth from actinium. Background Technology

[0002] Compared to the physical targeting of traditional radiotherapy, targeted radionuclide therapy offers higher selectivity for tumor cells and avoids radiation damage to normal tissue cells, making it an important clinical treatment for tumors, especially demonstrating unique advantages in small and scattered tumors. High linear energy transfer (LET) and short-range alpha particles can be used in targeted radionuclide therapy (TRNT). High LET ensures that most of the energy of the alpha particles is transferred to the target cells, while the short range ensures that the radionuclide is targeted to cancer cells without affecting other normal cells.

[0003] Ac-225 is one of the most promising alpha nuclides, with a half-life of 9.92 days. During its decay, it undergoes four alpha decays, releasing 27.5 MeV of energy. Its daughter nuclide, Bi-213, can also be used for targeted therapy. With a half-life of 45.59 minutes, Bi-213 produces 440 keV of gamma rays during decay (with a branching ratio of 26%), which can be used in single-photon emission computed emission computed tomography (SEPCT) to detect the distribution of nuclides in organisms. Due to its short half-life, Bi-213 cannot be manufactured and distributed directly to recipient sites. It is typically separated from the mixture using Ac-225 as the parent nuclide after decay equilibrium is reached.

[0004] The main method for separating Bi-213 involves loading an actinium solution onto a cation exchange resin AGMP-50 and eluting Bi with different eluents, such as 0.1 mol / L hydrochloric acid / sodium chloride, 0.1 mol / L hydroiodic acid, 0.3 mol / HCl, 0.3 mol / L HBr, or a mixture of hydroiodic acid and hydrochloric acid; or loading it onto a cation exchange resin DOWEX50 and eluting Bi with a 10⁻³-10⁻² DTPA solution at pH 1.8-2.2. Besides AGMP-50, Isolute SCX and Isolute SCX2 can also be used to separate Ac and Bi, avoiding damage to the organic separation material from radiation particles. Isolute SCX is made by functionalizing silica adsorbent with benzenesulfonic acid, while Isolute SCX2 is made by functionalizing silica with propylsulfonic acid. However, the separation process caused varying degrees of Ac-225 leakage. Ac mixed with Bi competed with Bi during labeling, resulting in a low labeling rate of Bi. Moreover, the energy generated by the decay of attached Ac-225 can break the chemical bond between it and the antibody. The disintegration of the antibody used to target cancer cells can lead to the distribution of Ac throughout the body, causing potential harm. Summary of the Invention

[0005] The purpose of this invention is to provide a method for separating bismuth from actinium, in order to solve the above-mentioned technical problems.

[0006] To achieve the above objective, the present invention provides a method for separating bismuth from actinium, the method comprising:

[0007] A hydrochloric acid or nitric acid solution containing actinium is passed through a cation exchange column and eluted with a first hydrochloric acid to obtain an eluent containing bismuth (Bi).

[0008] The eluent containing Bi was passed through a TK201 resin column to obtain Bi adsorbed on the TK201 resin column.

[0009] Bi adsorbed on the TK201 resin column is eluted with a second hydrochloric acid or nitric acid to obtain a Bi eluent.

[0010] The present invention also provides an apparatus for separating bismuth from actinium, the apparatus comprising:

[0011] The first obtaining unit is used to pass a hydrochloric acid / nitric acid solution containing actinium through a cation exchange column and elute with a first hydrochloric acid to obtain an eluent containing bismuth (Bi);

[0012] The second obtaining unit is used to pass the eluent containing Bi through a TK201 resin column to obtain Bi adsorbed on the TK201 resin column.

[0013] The third obtaining unit is used to elute Bi adsorbed on the TK201 resin column with a second hydrochloric acid or nitric acid to obtain Bi eluent.

[0014] The technical effects and advantages of this invention are as follows:

[0015] 1. This invention innovatively uses TK201 resin as a purification material for Bi. TK201 resin is synthesized based on a tertiary amine and doped with a small amount of a long-chain alcohol. Under certain concentrations of hydrochloric acid, it has specific adsorption on Bi, but no adsorption capacity for Ac and Fr. Therefore, it greatly reduces the content of Ac in Bi.

[0016] 2. This invention can also obtain Bi-213 with high chemical purity and radioactive purity.

[0017] Other features and advantages of the invention will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of the invention may be realized and obtained by means of the structures pointed out in the description and the drawings. Attached Figure Description

[0018] Figure 1 This is a flowchart of a method for separating bismuth from actinium. Detailed Implementation

[0019] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Furthermore, the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0020] It should be noted that the structures, proportions, sizes, etc., illustrated in the accompanying drawings are merely for illustrative purposes to aid those skilled in the art and to facilitate understanding and reading. They are not intended to limit the scope of the invention and therefore have no substantial technical significance. Any modifications to the structure, changes in proportions, or adjustments to size, without affecting the effectiveness and purpose of the invention, should still fall within the scope of the technical content disclosed herein. Furthermore, the terms "upper," "lower," "left," "right," "middle," and "one" used in this specification are merely for clarity and not intended to limit the scope of the invention. Changes or adjustments to their relative relationships, without substantially altering the technical content, should also be considered within the scope of the invention.

[0021] To address the shortcomings of existing technologies, this invention discloses a method for separating bismuth from actinium. This invention significantly reduces the leakage of Ac-225 on the exchange column, thereby reducing the Ac-225 content in the Bi-213 product. The following is in conjunction with... Figure 1 A method for separating bismuth from actinium is described in detail, the method comprising:

[0022] 1. Pass a hydrochloric acid or nitric acid solution containing actinium through a cation exchange column and elute with first hydrochloric acid to obtain an eluent containing bismuth (Bi).

[0023] Specifically, the packing material for the cation exchange column includes AG50W-X8 or any sulfonated styrene-divinylbenzene copolymer with a crosslinking degree greater than 4. Among them, resins with a higher degree of crosslinking have a larger adsorption capacity for the elements to be adsorbed, higher strength, and better selectivity.

[0024] Specifically, the particle size of cation exchange resin is 100-200 mesh, which has good selectivity for metal ions. The lower the mesh number, the larger the particle size and the worse the selectivity for elements.

[0025] Specifically, the height-to-diameter ratio of cation exchange columns is 5:1 to 8:1. The larger the height-to-diameter ratio, the better the separation effect, but at the same time, the flow rate is also slower.

[0026] Specifically, the concentration of hydrochloric acid or nitric acid is 0.1 mol / L.

[0027] Specifically, the hydrochloric acid or nitric acid solution containing actinium is fed onto the cation exchange column at a rate of 0.5-2.5 mL / min to ensure complete adsorption of metal ions by the cation exchange resin and to ensure that actinium is distributed as evenly as possible on the resin column, rather than remaining only at the top, which would cause localized damage to the resin particles from actinium decay α particles. The equilibrium time between Ac-225 and Bi-213 is approximately 5 hours; in fact, 90% of Bi-213 can be formed within 3 hours.

[0028] Specifically, the actinium solution has an acidity of 0.1 mol / L. Under low acidity, the hydrogen ion concentration is not high, and the exchange ions [H] on the resin are... + Only after exchanging with metal ions can all elements be adsorbed by the ion exchange resin.

[0029] Specifically, Bi on the cation exchange column is eluted with a 0.4-0.6 mol / L hydrochloric acid solution. At this acidity, the cation exchange resin has a weak adsorption capacity for Bi but still a strong adsorption capacity for Ac, so Bi can be eluted.

[0030] Specifically, elute 8-12 column volumes with a 0.4-0.6 mol / L hydrochloric acid solution to ensure that all Bi adhering to the resin is eluted. The elution rate should be 0.5-1 mL / min; too slow an elution rate will cause Bi tailing and increase the eluent volume.

[0031] 2. Pass the eluent containing Bi through a TK201 resin column to obtain Bi adsorbed on the TK201 resin column.

[0032] 3. Use hydrochloric acid or nitric acid to elute the Bi adsorbed on the TK201 resin column to obtain the Bi eluent.

[0033] Specifically, the Bi eluent is mixed with the same volume of 3 mol / L hydrochloric acid and passed through a TK201 resin column. Impurity elements flow out with the solution. Then, the Bi on the resin column is eluted with a second hydrochloric acid solution or nitric acid solution of 0.01-0.1 mol / L, with an elution volume of 6-8 column volumes.

[0034] The extraction resin column uses TK201 resin, which is synthesized based on a tertiary amine and doped with a small amount of a long-chain alcohol. The height-to-diameter ratio of the TK201 resin column is 4:1-7:1. A larger height-to-diameter ratio results in better separation, but a finer separation column can also affect the liquid flow rate. The particle size of the extraction resin is 100-150 μm. The choice of particle size is mainly related to the selectivity for elements; larger particle sizes result in lower selectivity, while smaller particle sizes result in higher selectivity.

[0035] In this process, the eluent containing Bi in the cation exchange resin flows through the extraction resin column at a flow rate equal to the rate generated by its own weight.

[0036] The adsorbed Bi was eluted with 0.01 mol / L second hydrochloric acid or nitric acid at a flow rate of 0.6-0.8 mL / min to ensure that all Bi on the column was eluted.

[0037] To better explain this scheme, examples and comparative examples are provided below. In this experiment, cerium (Ce) is used as an analogue of Ac. 3+ The ionic radius is 102 pm, similar to Ac. 3+ The ionic radii of the two molecules are close to 112 pm, and their chemical properties are similar, so the experimental results are reliable.

[0038] Example 1:

[0039] Prepare a Ce and Bi separation solution with the elemental composition at equilibrium of Ac-225 and Bi-213, and Fr-221(T) 1 / 2 =4.9m), At-217(T 1 / 2=32ms) Due to its short half-life, it rapidly decays into Bi-213 and is therefore not calculated. The solution atmosphere is 0.1mol / L hydrochloric acid solution, and the total solution volume is 10mL. After pretreatment with AG50W-X8 (100-200 mesh) cation exchange resin, the column was packed with a height-to-diameter ratio of 5:1. The solution to be separated was passed through the cation exchange column at a rate of 0.75mL / min, and the eluent 1 was collected.

[0040] A 0.4 mol / L hydrochloric acid solution was passed through a cation exchange resin at a volume of 15 mL and a rate of 0.75 mL / min. The resulting Bi eluent 1 was collected. 15 mL of a 3 mol / L hydrochloric acid solution was mixed with the Bi eluent and passed through an extraction resin column made of TK201 (100-150 μm) resin with a height-to-diameter ratio of 7:1 at a loading rate of 0.8 mL / min. The resulting effluent 2 was collected.

[0041] The 0.01 mol / L hydrochloric acid solution was passed through the extraction resin column at an elution rate of 0.8 mL / min. The volume of 0.01 mol / L hydrochloric acid used was 8 column volumes, resulting in Bi eluent 2, which is the final Bi product solution.

[0042] Example 2:

[0043] Prepare a Ce and Bi separation solution with the elemental composition at equilibrium of Ac-225 and Bi-213, and Fr-221(T) 1 / 2 =4.9m), At-217(T 1 / 2 =32ms) Due to its short half-life, it rapidly decays into Bi-213 and is therefore not calculated. The solution atmosphere is 0.1mol / L hydrochloric acid solution, and the total solution volume is 10mL. After pretreatment with DOWEX50W-X8 (100-200 mesh) cation exchange resin, the column was packed with a height-to-diameter ratio of 5:1. The solution to be separated was passed through the cation exchange column at a rate of 0.70mL / min, and the eluent 1 was collected.

[0044] A 0.4 mol / L hydrochloric acid solution was passed through a cation exchange resin at a volume of 15 mL and a rate of 0.75 mL / min. The resulting Bi eluent 1 was collected. 15 mL of a 3 mol / L hydrochloric acid solution was mixed with the Bi eluent and passed through an extraction resin column made of TK201 (100-150 μm) resin with a height-to-diameter ratio of 5:1 at a loading rate of 0.8 mL / min. The resulting effluent 2 was collected.

[0045] The 0.01 mol / L hydrochloric acid solution was passed through the extraction resin column at an elution rate of 0.8 mL / min. The volume of 0.01 mol / L hydrochloric acid used was 6 column volumes, resulting in Bi eluent 2, which is the final Bi product solution.

[0046] Example 3:

[0047] Prepare a Ce and Bi separation solution with the elemental composition at equilibrium of Ac-225 and Bi-213, and Fr-221(T) 1 / 2 =4.9m), At-217(T 1 / 2 =32ms) Due to its short half-life, it rapidly decays into Bi-213 and is therefore not calculated. The solution atmosphere is 0.1mol / L hydrochloric acid solution, and the total solution volume is 10mL. After pretreatment with AGMP-50 cation exchange resin (100-200 mesh), the column is packed with a height-to-diameter ratio of 6:1. The solution to be separated is passed through the cation exchange column at a rate of 0.70mL / min, and the eluent 1 is collected.

[0048] A 0.4 mol / L hydrochloric acid solution was passed through a cation exchange resin at a volume of 15 mL and a rate of 0.75 mL / min. The resulting Bi eluent 1 was collected. 15 mL of a 3 mol / L hydrochloric acid solution was mixed with the Bi eluent and passed through an extraction resin column made of TK201 (100-150 μm) resin with a height-to-diameter ratio of 6:1 at a loading rate of 0.8 mL / min. The resulting effluent 2 was collected.

[0049] The 0.01 mol / L hydrochloric acid solution was passed through the extraction resin column at an elution rate of 0.8 mL / min. The volume of 0.01 mol / L hydrochloric acid used was 6 column volumes, resulting in Bi eluent 2, which is the final Bi product solution.

[0050] Comparative Example 1

[0051] Prepare a Ce and Bi separation solution with the elemental composition at equilibrium of Ac-225 and Bi-213, and Fr-221(T) 1 / 2 =4.9m), At-217(T 1 / 2=32ms) Due to its short half-life, it rapidly decays into Bi-213 and is therefore not calculated. The solution atmosphere is 0.1mol / L hydrochloric acid solution, and the total solution volume is 10mL. After pretreatment with AG50W-X8 (100-200 mesh) cation exchange resin, the column was packed with a height-to-diameter ratio of 5:1. The solution to be separated was passed through the cation exchange column at a rate of 0.75mL / min, and the eluent 1 was collected. The prepared 0.5mol / L hydrochloric acid solution was passed through the cation exchange resin, with an elution volume of 6 column volumes and an elution rate of 0.75mL / min, and the resulting Bi eluent was collected.

[0052] Comparative Example 2

[0053] Prepare a Ce and Bi separation solution with the elemental composition at equilibrium of Ac-225 and Bi-213, and Fr-221(T) 1 / 2 =4.9m), At-217(T 1 / 2 =32ms) Due to its short half-life, it rapidly decays into Bi-213 and is therefore not calculated. The solution atmosphere is 0.1 mol / L hydrochloric acid solution, and the total solution volume is 10 mL. After pretreatment with DOWEX 50W-X8 (100-200 mesh) cation exchange resin, the column was packed with a height-to-diameter ratio of 5:1. The solution to be separated was passed through the cation exchange column at a rate of 0.70 mL / min, and the eluent 1 was collected. The prepared 0.4 mol / L hydrochloric acid solution was passed through the cation exchange resin, with an elution volume of 6 column volumes and an elution rate of 0.75 mL / min, and the resulting Bi eluent was collected.

[0054] Comparative Example 3

[0055] Prepare a Ce and Bi separation solution with the elemental composition at equilibrium of Ac-225 and Bi-213, and Fr-221(T) 1 / 2 =4.9m), At-217(T 1 / 2 =32ms) Due to its short half-life, it rapidly decays into Bi-213 and is therefore not calculated. The solution atmosphere is 0.1 mol / L hydrochloric acid solution, and the total solution volume is 10 mL. After pretreatment with AGMP-50 cation exchange resin (100-200 mesh), the column is packed with a height-to-diameter ratio of 6:1. The solution to be separated is passed through the cation exchange column at a rate of 0.70 mL / min, and the eluent 1 is collected. The prepared 0.1 mol / L hydrochloric acid solution is passed through the cation exchange resin, with an elution volume of 6 column volumes and an elution rate of 0.75 mL / min, and the resulting Bi eluent is collected.

[0056] project Ce leakage in Bi products Example 1 [Ce] 1.1 ± 0.1 ppm Example 2 [Ce] 0.3 ± 0.02 ppm Example 3 [Ce] 0.1 ± 0.01 ppm Comparative Example 1 [Ce] 11.3 ± 0.1 ppm Comparative Example 2 [Ce] 8.7 ± 0.1 ppm Comparative Example 3 [Ce] 4.2 ± 0.1 ppm

[0057] The present invention also provides an apparatus for separating bismuth from actinium, characterized in that the apparatus comprises: a first obtaining unit for passing an actinium-containing hydrochloric acid / nitric acid solution through a cation exchange column and eluting with a first hydrochloric acid to obtain an eluent containing bismuth (Bi); a second obtaining unit for passing the Bi-containing eluent through a TK201 resin column to obtain Bi adsorbed on the TK201 resin column; and a third obtaining unit for eluting the Bi adsorbed on the TK201 resin column with a second hydrochloric acid or nitric acid to obtain a Bi eluent.

[0058] Since the protection provided by this device is similar to that provided by the method described above, it will not be described in detail here. Please refer to the discussion section of the method described above for more information.

[0059] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for separating bismuth from actinium, characterized in that, The method includes: A hydrochloric acid or nitric acid solution containing actinium at a concentration of 0.1 mol / L was passed through a cation exchange column and eluted with a first hydrochloric acid to obtain an eluent containing bismuth (Bi). The process of passing a Bi-containing eluent through a TK201 resin column to obtain Bi adsorbed on the TK201 resin column includes: mixing the Bi-containing eluent with the same volume of 3 mol / L hydrochloric acid and passing it through a TK201 resin column; after impurities are effluent, Bi adsorbed on the TK201 resin column is obtained. Bi adsorbed on the TK201 resin column was eluted with a second hydrochloric acid or nitric acid to obtain a Bi eluent; The packing material of the cation exchange column includes: AG50W-X8 cation exchange resin or any sulfonated styrene-divinylbenzene copolymer with a crosslinking degree greater than 4, and the particle size of the cation exchange resin in the cation exchange column is 100-200 mesh. The elution rate of the first hydrochloric acid is 0.5-1 mL / min, and the concentration of the first hydrochloric acid is 0.4-0.6 mol / L; The loading rate of the hydrochloric acid or nitric acid solution containing actinium at a concentration of 0.1 mol / L is 0.5-2.5 mL / min; The concentration of the second hydrochloric acid or nitric acid is 0.01-0.1 mol / L, and the elution rate using the second hydrochloric acid or nitric acid is 0.6-0.8 mL / min.

2. The method according to claim 1, characterized in that, The height-to-diameter ratio of the cation exchange column is 5:1-8:

1.

3. The method according to claim 1, characterized in that, The volume of the first hydrochloric acid used for elution is 8-12 column volumes.

4. The method according to claim 1, characterized in that, The height-to-diameter ratio of the TK201 resin column is 4:1-7:1; the particle size of the resin in the TK201 resin column is 100-150 μm.

5. The method according to claim 1, characterized in that, The volume of the second hydrochloric acid or nitric acid used for elution is 6-8 column volumes.

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