A method for producing an ac-225 mother liquor by irradiation of a thorium target

Abstract

The application discloses a method for producing Ac-225 mother liquor by irradiating a thorium target, and comprises the following steps: dissolving the irradiated thorium target to obtain an irradiated thorium target solution; separating and removing thorium and Ac in the irradiated thorium target solution to obtain a Ra crude product liquid; passing the Ra crude product liquid through a TK102 resin column, washing the TK102 resin column with a 2.5-3.5 mol / L hydrochloric acid solution for 13-15 column volumes, and obtaining a Ra elution liquid; placing the Ra elution liquid for a set time, diluting the Ra elution liquid, and making the hydrochloric acid concentration in the Ra elution liquid reach 0.01-0.05 mol / L to obtain a dilution liquid; passing the dilution liquid through a TK101 resin column, collecting the effluent; washing the TK101 resin column with 0.01-0.05 mol / L hydrochloric acid, and collecting the washing liquid; and mixing the effluent and the washing liquid to obtain the Ac-225 mother liquor product.

Description

Technical Field

[0001] This invention belongs to the field of Ac-225 mother liquor preparation technology, specifically relating to a method for producing Ac-225 mother liquor by irradiating a thorium target. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] Targeted Alpha Therapy (TAT) is a therapeutic approach based on the combination of a radionuclide that emits alpha particles and a tumor-selective carrier molecule. This carrier targets the radionuclide to the lesion or affected area, where the decaying radionuclide produces alpha particles that damage the lesion, thus achieving the therapeutic goal. Among the radionuclides used for targeted therapy, alpha nuclides, compared to beta nuclides and Auger electron-emitting nuclides, are characterized by high radiation energy, short range, strong radiation biological effects, and high cytotoxicity.

[0004] Ac-225 is a promising TAT radionuclide with a half-life of 9.9 days. During its decay to the stable nuclide Bi-209, it undergoes four alpha decays and two beta decays, releasing alpha particles with a total energy of 27.5 MeV, which can effectively kill cancer cells. Currently, there are three main methods for producing Ac-225 internationally:

[0005] (1) U-233 in spent fuel decays rapidly to produce Th-229 (T 1 / 2 =7880), Ac-225, as a second-generation offspring of Th-229, can be separated from it.

[0006] (2) Producing Ac-225 by irradiating Ra-226 solution with protons or gamma rays.

[0007] (3) Proton irradiation of Th-232 produces Ac-225, or its other spallation product Ra-225 decays to produce Ac-225.

[0008] Due to current restrictions on U-223 and extremely limited reserves of Ra-226, accelerator irradiation of thorium targets to produce Ac-225 has become the primary source of Ac-225 nuclides. Proton irradiation of thorium targets to produce Ac-225 generates over seventy elements and hundreds of nuclides, resulting in a complex source term composition. Furthermore, the directly generated Ac-225 product contains 0.1%-0.2% Ac-227, whose beta rays can damage human tissue, and Ac-227 cannot be removed from the Ac-225 product.

[0009] Furthermore, when Th-232 is irradiated with protons, its spallation products include Ra-225. When Ra-225 decays to form Ac-225, Ac-225 without Ac-227 can be obtained. However, when extracting Ac-225 from radium mother liquor, there may be a problem of incomplete penetration of the parent nuclide Ra-225, resulting in insufficient radioactive purity of Ac-225 and a low drug labeling rate. Summary of the Invention

[0010] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a method for producing Ac-225 mother liquor by irradiating a thorium target, which can effectively reduce the content of the parent nuclide in the Ac-225 product and improve the purity of Ac-225.

[0011] To achieve the above objectives, the present invention is implemented through the following technical solution:

[0012] A method for producing Ac-225 mother liquor by irradiating a thorium target includes the following steps:

[0013] After dissolving the proton-irradiated thorium target, an irradiated thorium target solution is obtained;

[0014] Thorium and Ac were separated and removed from the irradiated thorium target solution to obtain crude Ra product solution;

[0015] After passing the crude Ra product solution through a TK102 resin column, the TK102 resin column is washed with 2.5-3.5 mol / L hydrochloric acid solution for 13-15 column volumes to obtain Ra eluent. If the washing volume is too small, Ra cannot be completely washed; if it is too large, the specific activity of Ra will decrease.

[0016] After the Ra eluent has been left to stand for a set time, it is diluted to make the hydrochloric acid concentration reach 0.01-0.05 mol / L to obtain the diluted solution.

[0017] Pass the diluted solution through a TK101 resin column and collect the effluent;

[0018] The TK101 resin column was washed with 0.01-0.05 mol / L hydrochloric acid, and the washing solution was collected.

[0019] The Ac-225 mother liquor product is obtained by mixing the effluent and the washing liquid.

[0020] The inventors discovered during experiments that the spallation reaction caused by proton irradiation of a thorium target generates various elements in the same group as radium, such as Ca, Sr, and Ba. Ra has similar chemical properties to these three elements, making it difficult to remove and readily entering the crude Ra product solution. The Ca, Sr, and Ba elements themselves, or their generated daughter products, affect the purity of Ac-225. To obtain a qualified Ac-225 product, it is necessary to remove Ca, Sr, and Ba elements from the crude Ra product solution.

[0021] Through repeated experiments, it was found that when using the TK102 resin column as the purification resin column, impurity elements such as Ba, Sr, Pb, and Ca are adsorbed onto the TK102 resin column along with Ra. However, when using a 2.5-3.5 mol / L hydrochloric acid solution as the eluent, Ra can be selectively eluted from the TK102 resin column, thereby separating and removing elements such as Ca, Sr, and Ba from Ra to obtain a purified Ra eluent. Beyond this concentration range, the elution efficiency of Ra decreases to varying degrees.

[0022] Separating Ac-225 from Ra is not difficult, but Ra is easily lost through the process, resulting in a high Ra content in Ac and reducing the purity of the Ac-225 product.

[0023] In this invention, the Ra eluent is diluted to a hydrochloric acid concentration of 0.01-0.05 mol / L. At this acidity, the TK101 resin exhibits strong adsorption capacity for Ra. When the diluted solution is passed through the TK101 resin, trace impurities in Ra, such as Sr, Ba, and Pb, are adsorbed onto the TK101 resin column. Ra and its decay products, such as Bi and Pb, are also adsorbed onto the TK101 resin column, while most Ac-225 remains in the effluent.

[0024] Through experimentation, the inventors discovered that when using TK101 resin for separation and purification, although most Ac-225 remains in the effluent, some Ac-225 is still adsorbed onto the TK101 resin, resulting in waste. However, by washing the TK101 resin column with 0.01-0.05 mol / L hydrochloric acid, the Ac-225 can be selectively eluted. Mixing the effluent and washing solution yields a high-purity Ac-225 product. Outside this concentration range, the elution efficiency of Ac decreases to varying degrees. Furthermore, compared to other methods using TK221 or DGA resin to separate Ra and Ac, this method has the advantage of producing a lower acidity Ac product solution, making it suitable for subsequent drug labeling studies. It avoids the problems associated with acid adjustment, which can lead to decreased specific activity and loss of elemental products, as will be explained in the comparative examples.

[0025] In some embodiments, the resin particle size of TK102 resin is 100-150 μm, and the extractant loaded on the surface of the resin particles is di-tert-butyldicyclohexyl-18-crown-6.

[0026] Preferably, the flow rate of the crude Ra product liquid through the TK102 resin column is 0.5-1.5 mL / min.

[0027] Preferably, when washing the TK102 resin column with a 2.5-3.5 mol / L hydrochloric acid solution, the flow rate of the hydrochloric acid solution is 0.5-1.5 mL / min.

[0028] In some embodiments, the Ra eluent is diluted after being left to stand for 15-19 days.

[0029] Preferably, the Ra eluent is diluted after being left to stand for 17 days (at which point the activity of Ac-225 in it reaches its maximum).

[0030] In some embodiments, the TK101 resin has a resin particle size of 100-150 μm, and the loaded extractant is a mixture of di-tert-butyldicyclohexyl-18-crown-6 and di(2-ethylhexyl) phosphate.

[0031] Preferably, when passing the diluent through the TK101 resin column, the loading rate of the diluent in the TK101 resin column is 0.5-1.5 mL / min.

[0032] Further preferably, the loading speed and elution speed of the TK101 resin column are both 0.7-1.2 mL / min.

[0033] The beneficial effects achieved by one or more embodiments of the present invention described above are as follows:

[0034] When using a TK102 resin column as the purification resin column, impurity elements such as Ba, Sr, Pb, and Ca are adsorbed onto the TK102 resin column along with Ra. When a 2.5-3.5 mol / L hydrochloric acid solution is selected as the eluent, Ra can be selectively eluted from the TK102 resin column, and elements such as Ca, Sr, and Ba can be separated and removed from Ra to obtain purified Ra eluent.

[0035] When separating Ac-225 from Ra, Ra is easily lost through the eluent, resulting in a high Ra content in Ac and reducing the purity of the Ac-225 product. This invention dilutes the Ra eluent to a hydrochloric acid concentration of 0.01-0.05 mol / L. At this acidity, the TK101 resin has a strong adsorption capacity for Ra. Passing the diluted solution through the TK101 resin, trace impurities in Ra such as Sr, Ba, and Pb are adsorbed onto the TK101 resin column. Ra and its decay products such as Bi and Pb are also adsorbed onto the TK101 resin column, while most Ac-225 remains in the effluent. Washing the TK101 resin column with 0.01-0.05 mol / L hydrochloric acid allows for selective elution of the Ac-225. Mixing the effluent and washing solution yields a high-purity Ac-225 product. The obtained Ac product solution has a low acidity, which is suitable for subsequent drug labeling studies without the hassle of acid adjustment, which can lead to problems such as reduced specific activity and loss of elemental products. Detailed Implementation

[0036] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0037] The present invention will be further described below with reference to the embodiments.

[0038] Example 1

[0039] Since isotopes of Ac and Ra are difficult to obtain, La and Ba were used to simulate the chemical properties of Ac and Ra, respectively, in simulation experiments. Ba and Ra are elements in the same group with ionic radii of 135 pm and 143 pm, respectively. They have similar electronic configurations and chemical properties. La and Ac have ionic radii of 106 pm and 112 pm, respectively. They are also in the same group and have similar chemical properties. Existing literature also uses these two elements to simulate the properties of Ra and Ac. See: Two-step separation of Th, La and Ba using combined chromatographic columns, Published: 16 January 2023; Volume 332, pages 1245-1252, (2023); Cite this article.

[0040] The specific operating steps are as follows:

[0041] First, a simulated feed solution was prepared based on the ratio of Sr, Ba, Pb, and La elements obtained from proton irradiation of a thorium target. The concentrations were Sr-50ppm, Ba-32ppm, Pb-50ppm, and La-2ppm, respectively. The solution acidity was 3mol / L nitric acid, and the solution volume was 5mL. The particle size of the TK102 resin column (Triskem) was 100-150 micrometers. The extractant loaded on the surface of the resin particles was di-tert-butyldicyclohexyl-18-crown-6. The resin column volume was 1mL, and the column loading rate and washing flow rate were both 1mL / min.

[0042] The rinsing solution was a 3 mol / L hydrochloric acid solution, and the rinsing volume was 10 mL.

[0043] Prepare a 3 mL simulated feed solution after Ra-225 and Ac-225 reach equilibrium: Sr-0.5 ppm, Ba-320 ppm, Pb-0.2 ppm, La-5 ppm, Bi-5 ppm, with an acidity of 0.05 mol / L hydrochloric acid. Pass the simulated feed solution through TK101 resin (Triskem), with a resin particle size of 100-150 micrometers. The loaded extractant is a mixture of di-tert-butyldicyclohexyl-18-crown-6 and di(2-ethylhexyl) phosphate, and the resin column volume is 2 mL.

[0044] The column loading rate was 0.5 mL / min, followed by washing with 0.05 mol / L hydrochloric acid at a rate of 0.5 mL / min for a washing volume of 13 mL.

[0045] The final decontamination coefficient of La for Ba was approximately 1500, for Pb approximately 800, and for Bi approximately 3200. The purity of La was 99.93%, and the recovery rate was 95%.

[0046] Example 2

[0047] First, a simulated solution was prepared based on the ratio of Sr, Ba, Pb, and La elements obtained from proton irradiation of a thorium target. The concentrations were Sr-50ppm, Ba-32ppm, Pb-50ppm, and La-2ppm, respectively. The solution acidity was 3mol / L nitric acid, and the solution volume was 5mL.

[0048] The TK102 resin column has a particle size of 100-150 micrometers. The extractant loaded on the surface of the resin particles is di-tert-butyldicyclohexyl-18-crown-6. The resin column volume is 1 mL, and the loading flow rate and washing flow rate are both 1.5 mL / min.

[0049] The rinsing solution was a 2.5 mol / L hydrochloric acid solution, and the rinsing volume was 15 mL.

[0050] Prepare 3 mL of simulated feed solution after Ra-225 and Ac-225 reach equilibrium: Sr-0.5ppm, Ba-320ppm, Pb-0.2ppm, La-5ppm, Bi-5ppm, with an acidity of 0.05mol / L hydrochloric acid;

[0051] The simulated feed solution was passed through TK101 resin with a particle size of 100-150 micrometers. The loaded extractant was a mixture of di-tert-butyldicyclohexyl-18-crown-6 and di(2-ethylhexyl) phosphate, and the resin column volume was 2 mL.

[0052] The column loading rate was 0.5 mL / min, followed by washing with 0.03 mol / L hydrochloric acid at a rate of 1 mL / min for a washing volume of 10 mL.

[0053] The final decontamination coefficient of La was 1400 for Ba, 830 for Pb, and 3220 for Bi. The purity of La was 99.95%, and the recovery rate was 96%.

[0054] Comparative Example 1

[0055] A simulated feed solution was prepared after Ra-225 and Ac-225 reached equilibrium, with Sr -0.5ppm, Ba -320ppm, Pb -0.2ppm, La -5ppm, and Bi -5ppm. The solution acidity was 0.5mol / L nitric acid. The simulated feed solution was passed through a nitrate-type cation exchange resin, specifically commercially available AG50W-X4 (Bio-Rad) resin with a particle size of 200-400 mesh, at a loading rate of 1mL / min. It was then washed with 2.4mol / L hydrochloric acid at a washing rate of 1.5mL / min for a washing volume of 40mL. Ra, Sr, Ba, and Pb were preferentially eluted, followed by Ac and Bi, yielding the Ac product solution. The final decontamination factor for La was approximately 400 for Ba, approximately 300 for Pb, and approximately 10 for Bi. The purity of La was approximately 98%, and the recovery rate was 94%.

[0056] Comparative Example 2

[0057] A simulated feed solution was prepared after Ra-225 and Ac-225 reached equilibrium, with Sr -0.5ppm, Ba -320ppm, Pb -0.2ppm, La -5ppm, and Bi -5ppm. The solution acidity was 4 mol / L nitric acid. The simulated feed solution was passed through TK221 resin (Triskem) with a mixture of diethanolamide and phosphine oxide as the loading extractant. The resin particle size was 100-150 μm, and the column loading speed was 1 mL / min. The solution was then washed with 4 mol / L nitric acid at a washing rate of 0.5 mL / min for a washing volume of 20 mL. Ra, Sr, Ba, and Pb were washed away. Finally, the column was eluted with 40 mL of 10 mol / L nitric acid to obtain the Ac(La) product solution. The final purity of La was 99.3%, and the recovery rate was 85%. However, the acidity of the obtained Ac(La) was too high, posing a significant challenge to the subsequent acid adjustment process.

[0058] Comparative Example 3

[0059] A simulated feed solution was prepared after Ra-225 and Ac-225 reached equilibrium, with Sr -0.5 ppm, Ba -320 ppm, Pb -0.2 ppm, La -5 ppm, and Bi -5 ppm. The solution acidity was 4 mol / L nitric acid. The simulated feed solution was passed through DGA resin (Triskem) with diethanolamide as the loading extractant. The resin particle size was 100-150 μm, and the column loading speed was 1 mL / min. The column was then washed with 4 mol / L nitric acid at a washing speed of 0.5 mL / min for a washing volume of 10 mL, eluting impurities such as Ra and Ba. Next, 10 mL of 10 mol / L nitric acid was used for elution, eluting Sr and Pb. Finally, 20 mL of 10 mol / L nitric acid was used to elute the column to obtain the Ac(La) product solution. However, the elution curves of Sr and Pb partially overlapped with those of Ac(La), resulting in a low recovery rate of Ac(La). The final purity of La was 99.68%, and the recovery rate was 78%. The acidity of Ac(La) obtained by this method is too high, which poses a great challenge to the subsequent acid adjustment process.

[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for producing Ac-225 mother liquor by irradiating a thorium target, characterized in that: Includes the following steps: After dissolving the proton-irradiated thorium target, an irradiated thorium target solution is obtained; Thorium and Ac were separated and removed from the irradiated thorium target solution to obtain crude Ra product solution; After passing the crude Ra product solution through a TK102 resin column, the TK102 resin column is washed with 2.5-3.5 mol / L hydrochloric acid solution for 13-15 column volumes to obtain Ra eluent. After the Ra eluent has been left to stand for a set time, it is diluted to make the hydrochloric acid concentration reach 0.01-0.05 mol / L to obtain the diluted solution. Pass the diluted solution through a TK101 resin column and collect the effluent; The TK101 resin column was washed with 0.01-0.05 mol / L hydrochloric acid, and the washing solution was collected. The Ac-225 mother liquor product is obtained by mixing the effluent and the washing liquid.

2. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 1, characterized in that: The TK102 resin has a particle size of 100-150μm, and the extractant loaded on the surface of the resin particles is di-tert-butyldicyclohexyl-18-crown-6.

3. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 2, characterized in that: The flow rate of the crude Ra product liquid through the TK102 resin column is 0.5-1.5 mL / min.

4. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 2, characterized in that: When washing the TK102 resin column with a 2.5-3.5 mol / L hydrochloric acid solution, the flow rate of the hydrochloric acid solution should be 0.5-1.5 mL / min.

5. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 1, characterized in that: After the Ra rinsing solution has been left to stand for 15-19 days, it should be diluted.

6. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 5, characterized in that: After the Ra rinsing solution was left to stand for 17 days, it was diluted.

7. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 1, characterized in that: The TK101 resin has a particle size of 100-150 μm, and the loaded extractant is a mixture of di-tert-butyldicyclohexyl-18-crown-6 and di(2-ethylhexyl) phosphate.

8. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 7, characterized in that: The loading rate of the TK101 resin column is 0.5-1.5 mL / min.

9. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 8, characterized in that: The rinsing rate of the TK101 resin column is 0.7-1.2 mL / min.

10. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 1, characterized in that: When passing the diluent through a TK101 resin column, the loading rate of the diluent in the TK101 resin column is 0.7-1.2 mL / min.