Method for producing Ac-225 mother liquor by irradiating thorium target

Abstract

The invention discloses a method for producing an Ac-225 mother solution by irradiating a thorium target, which comprises the following steps: dissolving a proton irradiation thorium target to obtain an irradiation thorium target dissolving solution; separating and removing thorium and Ac in the irradiation thorium target dissolving solution to obtain an Ra crude product solution; enabling the Ra crude product liquid to pass through a TK102 resin column, and washing the TK102 resin column by 13-15 column volumes with a 2.5-3.5 mol / L hydrochloric acid solution to obtain Ra leacheate; after the Ra leacheate is placed for a set time, the Ra leacheate is diluted, the concentration of hydrochloric acid in the Ra leacheate reaches 0.01-0.05 mol / L, and a diluent is obtained; enabling the diluent to pass through a TK101 resin column, and collecting effluent; washing the TK101 resin column by using 0.01-0.05 mol / L hydrochloric acid, and collecting a washing solution; and mixing the effluent and the washing liquid to obtain an Ac-225 mother liquor product.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of Ac-225 mother liquor, and in particular relates to a method for producing Ac-225 mother liquor by irradiating a thorium target. Background Art

[0002] The statements herein merely provide background information related to the present invention and do not necessarily constitute prior art.

[0003] Targeted Alpha Therapy (TAT) is a treatment method based on the combination of alpha-particle-emitting radionuclides and tumor-selective carrier molecules. As a targeted cancer cell carrier, the radionuclides are targeted to the lesions or diseased areas through the carriers. The radionuclides decay to produce alpha particles that damage the diseased areas to achieve the purpose of treatment. Among the radionuclides used for targeted therapy, alpha radionuclides have the characteristics of high radiation energy, short range, radiation biological effects and strong cytotoxicity compared to beta radionuclides and Auger electron-emitting radionuclides.

[0004] Among them, Ac-225 is a very promising TAT radionuclide with a half-life of 9.9 days. In the process of decaying to the stable nuclide Bi-209, it undergoes 4 alpha decays and 2 beta decays, releasing alpha particles with a total energy of 27.5 MeV, which can effectively kill cancer cells. At present, there are three main methods for producing Ac-225 internationally:

[0005] (1) U-233 in spent fuel will decay quickly to produce Th-229 (Th 1 / 2 =7880 years), Ac-225, as the second-generation progeny of Th-229, can be separated from it.

[0006] (2) Proton or gamma ray irradiation of Ra-226 solution to produce Ac-225.

[0007] (3) Using protons to irradiate Th-232 to produce Ac-225, or waiting for its other spallation product, Ra-225, to decay and produce Ac-225.

[0008] Due to the current control restrictions on U-223 and the extremely small stock of Ra-226, the production of Ac-225 by accelerator irradiation of thorium targets has become the main source of Ac-225 nuclides. When proton irradiation of thorium targets produces Ac-225, more than seventy elements and hundreds of nuclides are produced, and the source term composition is complex. In addition, the directly generated Ac-225 product contains 0.1%-0.2% Ac-227. The beta rays emitted by Ac-227 can cause damage to human tissues, and Ac-227 cannot be removed from the Ac-225 product.

[0009] In addition, when Th-232 is irradiated with protons, its spallation products include Ra-225. When Ra-225 decays to generate 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 leakage of the parent nuclide Ra-225, resulting in insufficient radioactivity purity of Ac-225 and a low drug labeling rate. Summary of the invention

[0010] In view of the shortcomings of the prior art, the purpose of the present 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] In order to achieve the above object, the present invention is implemented through the following technical solutions:

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

[0013] After dissolving the proton irradiated thorium target, an irradiated thorium target dissolved liquid is obtained;

[0014] Separating and removing thorium and Ac from the irradiated thorium target dissolution solution to obtain a Ra crude product solution;

[0015] After the Ra crude product solution passes through the 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 the Ra eluent. If the washing volume is too small, the Ra cannot be completely eluted, and if it is too large, the specific activity of Ra is reduced;

[0016] After the Ra eluent is placed for a set time, the Ra eluent is diluted so that the hydrochloric acid concentration therein reaches 0.01-0.05 mol / L to obtain a diluted solution;

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

[0018] Wash the TK101 resin column with 0.01-0.05 mol / L hydrochloric acid and collect the washing liquid;

[0019] The effluent and the washing liquid are mixed to obtain the Ac-225 mother liquor product.

[0020] The inventors found in experiments that the spallation reaction caused by proton irradiation of thorium target generates a variety of radium homologues, such as Ca, Sr, Ba and other elements. Ra has similar chemical properties to these three elements and is difficult to remove, but easily enters the Ra crude product solution. The elements Ca, Sr, Ba and other elements themselves or the generated daughters affect the purity of Ac-225. In order to prepare qualified Ac-225 products, it is necessary to remove the elements Ca, Sr, Ba and other elements in the Ra crude product solution.

[0021] After repeated tests, it was found that when TK102 resin column was selected as the purification resin column, impurity elements such as Ba, Sr, Pb, Ca and Ra were adsorbed on the TK102 resin column together. When 2.5-3.5 mol / L hydrochloric acid solution was selected as the eluent, Ra could be selectively eluted from the TK102 resin column, and then elements such as Ca, Sr, Ba and others could be separated and removed from Ra to obtain the purified Ra eluent. Beyond this concentration range, the elution efficiency of Ra decreased to varying degrees.

[0022] It is not difficult to separate Ac-225 from Ra, but the Ra element is easy to leak through, resulting in a higher Ra content in Ac and reducing the product purity of Ac-225.

[0023] The present invention dilutes the Ra eluent so that the hydrochloric acid concentration reaches 0.01-0.05 mol / L. At this acidity, the TK101 resin has a strong adsorption capacity for Ra. The diluted solution passes through the TK101 resin, and trace impurities in Ra such as Sr, Ba, Pb and other elements are adsorbed on the TK101 resin column, and Ra and its decay daughters such as Bi and Pb are also adsorbed on the TK101 resin column, and most of Ac-225 remains in the effluent.

[0024] The inventors have found through experiments that when TK101 resin is used for separation and purification, although most of the Ac-225 remains in the effluent, some Ac-225 is still adsorbed on the TK101 resin, resulting in a waste of Ac-225. When 0.01-0.05mol / L hydrochloric acid is used to wash the TK101 resin column, the Ac-225 above can be selectively eluted, and the effluent and the washing liquid are mixed to obtain a high-purity Ac-225 product. Beyond this concentration range, the elution efficiency of Ac decreases to varying degrees. And compared with other methods of separating Ra and Ac using TK221 resin or DGA resin, the advantage of this method is that the acidity of the Ac product solution is low, which is suitable for later drug labeling research, and there is no trouble with acid adjustment. The acid adjustment process will bring about problems such as reduced specific activity and loss of elemental products, which will be explained in the comparative example.

[0025] In some embodiments, the 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 Ra crude product solution through the TK102 resin column is 0.5-1.5 mL / min.

[0027] Preferably, when a 2.5-3.5 mol / L hydrochloric acid solution is used to wash the TK102 resin column, 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 the Ra eluent is allowed to stand for 15-19 days.

[0029] Preferably, after the Ra eluent is left for 17 days (when the activity of Ac-225 therein reaches a maximum), the Ra eluent is diluted.

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

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

[0032] More 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 are as follows:

[0034] When TK102 resin column is selected as the purification resin column, impurity elements such as Ba, Sr, Pb, Ca and Ra are adsorbed on the TK102 resin column together. When 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 then elements such as Ca, Sr, Ba can be separated and removed from Ra to obtain the purified Ra eluent.

[0035] When separating Ac-225 from Ra, the Ra element is easy to leak through, resulting in a high Ra content in Ac, which reduces the product purity of Ac-225. The present invention dilutes the Ra eluent so that the hydrochloric acid concentration therein reaches 0.01-0.05 mol / L. At this acidity, the TK101 resin has a strong adsorption capacity for Ra. The dilution is passed through the TK101 resin, and trace impurities such as Sr, Ba, Pb and other elements in Ra are adsorbed on the TK101 resin column, and Ra and its decay daughters such as Bi and Pb are also adsorbed on the TK101 resin column, and most of the Ac-225 remains in the effluent. When the TK101 resin column is washed with 0.01-0.05 mol / L hydrochloric acid, the Ac-225 above can be selectively eluted, and the effluent and the washing liquid are mixed to obtain a high-purity Ac-225 product. The obtained Ac product solution has a low acidity and is suitable for subsequent drug labeling research without the trouble of acid adjustment, which would lead to problems such as reduced specific activity and loss of elemental products. DETAILED DESCRIPTION

[0036] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0037] The present invention will be further described below in conjunction with the embodiments.

[0038] Example 1

[0039] Since the isotopes of Ac and Ra are difficult to obtain, La and Ba are used to simulate the chemical properties of Ac and Ra for simulation experiments. Ba and Ra are elements of the same group, with ionic radii of 135pm and 143pm respectively, similar electronic configurations and chemical properties; the ionic radii of La and Ac are 106pm and 112pm respectively, and they belong to the same group with 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: 16January2023; Volume 332, pages1245-1252, (2023); Cite this article.

[0040] The specific steps are as follows:

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

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

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

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

[0045] Finally, the decontamination coefficient of Ba in La is about 1500, the decontamination coefficient of Pb is about 800, the decontamination coefficient of Bi is about 3200, the purity of La is 99.93%, and the recovery rate is 95%.

[0046] Example 2

[0047] First, a simulated solution was prepared according to the ratio of the Sr, Ba, Pb, and La element contents obtained by proton irradiation of the 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 particle size of the TK102 resin column is 100-150 microns, the extractant loaded on the surface of the resin particles is di-tert-butyldicyclohexyl-18-crown-6, the volume of the resin column is 1 mL, and the column flow rate and washing flow rate are both 1.5 mL / min.

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

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

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

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

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

[0054] Comparative Example 1

[0055] Prepare a simulated feed solution after Ra-225 and Ac-225 reach equilibrium, Sr-0.5ppm, Ba-320ppm, Pb-0.2ppm, La-5ppm, Bi-5ppm, the solution acidity is 0.5mol / L nitric acid, pass the simulated feed solution through a nitrate-type cationic resin, the resin is a common commercially available resin AG50W-X4 (Bio-Rad), the resin particle size is 200-400 mesh, the column speed is 1mL / min, and then washed with 2.4mol / L hydrochloric acid, the washing speed is 1.5mL / min, the washing volume is 40mL, Ra, Sr, Ba, Pb will be eluted first, and then Ac and Bi will be eluted to obtain Ac product solution. Finally, the decontamination coefficient of Ba in La is about 400, the decontamination coefficient of Pb is about 300, the decontamination coefficient of Bi is about 10, the purity of La is about 98%, and the recovery rate is 94%.

[0056] Comparative Example 2

[0057] Prepare a simulated liquid after Ra-225 and Ac-225 reach equilibrium, Sr-0.5ppm, Ba-320ppm, Pb-0.2ppm, La-5ppm, Bi-5ppm, the acidity of the solution is 4mol / L nitric acid, pass the simulated liquid through TK221 resin (Triskem), the loaded extractant is a mixture of diethanolamide and phosphine oxide, the resin particle size is 100-150μm, the column speed is 1mL / min, then wash with 4mol / L nitric acid, the washing speed is 0.5mL / min, the washing volume is 20mL, Ra, Sr, Ba, Pb will be washed down, and finally elute the column with 40mL 10mol / L nitric acid to obtain the Ac(La) product solution. The final purity of La is 99.3%, and the recovery rate is 85%. However, the acidity of the obtained Ac(La) is too high, which brings great challenges to the subsequent acid adjustment process.

[0058] Comparative Example 3

[0059] Prepare a simulated feed solution after Ra-225 and Ac-225 reach equilibrium, Sr-0.5ppm, Ba-320ppm, Pb-0.2ppm, La-5ppm, Bi-5ppm, the solution acidity is 4mol / L nitric acid, pass the simulated feed solution through DGA resin (Triskem), the loading extractant is diethanolamide, the resin particle size is 100-150μm, the column speed is 1mL / min, then wash with 4mol / L nitric acid, the washing speed is 0.5mL / min, the washing volume is 10mL, and impurities such as Ra and Ba will be eluted. Then elute with 10mL10mol / L nitric acid, Sr and Pb will be eluted, and finally elute the column with 20mL 10mol / L nitric acid to obtain the product solution of Ac(La), but the elution products of Sr and Pb partially overlap with the elution curve of Ac(La), resulting in a low recovery rate of Ac(La). The final purity of La is 99.68%, and the recovery rate is 78%. The acidity of Ac(La) obtained by this method is too high, which brings great challenges to the subsequent acid adjustment process.

[0060] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for producing Ac-225 mother liquor by irradiating a thorium target, characterized in that: The steps include: After dissolving the proton irradiated thorium target, an irradiated thorium target dissolved liquid is obtained; Separating and removing thorium and Ac from the irradiated thorium target dissolution solution to obtain a Ra crude product solution; After the Ra crude product solution passes through the TK102 resin column, the TK102 resin column is washed with a 2.5-3.5 mol / L hydrochloric acid solution for 13-15 column volumes to obtain a Ra eluent; After the Ra eluent is placed for a set time, the Ra eluent is diluted so that the hydrochloric acid concentration therein reaches 0.01-0.05 mol / L to obtain a diluted solution; Pass the diluted solution through TK101 resin column and collect the effluent; Wash the TK101 resin column with 0.01-0.05 mol / L hydrochloric acid and collect the washing liquid; The effluent and the washing liquid are mixed to obtain the Ac-225 mother liquor product.

2. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 1, characterized in that: The particle size of TK102 resin is 100-150 μm, and the extractant loaded on the surface of the resin particles is di-tert-butyl dicyclohexyl-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 Ra crude product solution 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 a 2.5-3.5 mol / L hydrochloric acid solution is used to wash the TK102 resin column, the flow rate of the hydrochloric acid solution is 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 eluent has been left for 15-19 days, the Ra eluent is 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 eluent was left to stand for 17 days, the Ra eluent was diluted.

7. The method for producing Ac-225 mother liquor by irradiating a thorium target according to claim 1, characterized in that: The particle size of TK101 resin is 100-150 μm, and the loaded extractant is a mixture of di-tert-butyl dicyclohexyl-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 speed of TK101 resin column is 0.5-1.5mL / min.

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

10. When the diluent is passed through the TK101 resin column, the loading speed of the diluent in the TK101 resin column is 0.7-1.2 mL / min.