A method for preparing carrier-free lutetium-177 by multistage continuous separation and purification

Abstract

The application discloses a method for preparing carrier-free Lutetium-177 by multistage continuous separation and purification, and belongs to the field of preparation of radioisotopes. 177 Target material containing Lu 176 Yb2O3 is heated and dissolved to prepare a first nitric acid solution containing the target material; after the first nitric acid solution containing the target material is filtered and loaded onto a separation column, the separation column is eluted with a second nitric acid solution and a third nitric acid solution, the effluent is loaded onto a conversion column again through a purification column; and the conversion column is eluted with a first nitric acid solution and a hydrochloric acid solution. The method for preparing carrier-free Lutetium-177 by multistage continuous separation and purification is simple and easy to operate, realizes multistage and continuous separation for preparing carrier-free Lutetium-177, significantly improves the recovery rate of Lutetium-177, and provides a feasible and efficient method for efficient preparation of carrier-free Lutetium-177.

Description

Technical Field

[0001] This invention relates to the field of radioisotope preparation, specifically to a method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification. Background Technology

[0002] 177 Lu, as a medical radioactive isotope, possesses excellent nuclear physics properties: a suitable half-life (6.6 days), beta-ray energy (average energy 149 keV), and gamma-ray energy (208.4 keV, 10.4%). It is used in radioligand therapy. 177 Lu-labeled radiopharmaceuticals have become a hot topic in nuclear medicine research and application. Currently, two drugs have been approved by the FDA for clinical use in the treatment of neuroendocrine tumors and metastatic trend-resistant prostate cancer, with significant effects.

[0003] 177 Lu can be divided into those with carriers 177 Lu and carrier-free lutetium-177, among which are used for radioligand therapy. 177 Lu requires high specific activity, therefore it is mostly found in carrier-free lutetium-177. 177 The nuclear reaction for the preparation of Lu is 176 Yb(n,γ) 177 Yb, 177 Yb undergoes β-decay (T) 1 / 2 =1.9h) generated 177 Lu. Since Yb ​​and Lu are two adjacent lanthanide heavy rare earth elements with extremely similar physicochemical properties, their separation is quite difficult. Furthermore, the preparation of Curie-class materials in a medium-flux reactor... 177 Lu process 177 The chemical mass of Lu is generally in the tens of micrograms, while 176 The chemical mass of Yb ranges from several hundred milligrams to grams, and the Yb / Lu mass ratio is typically around 10. 3 -10 5 It can be seen that in a radioactive environment, from a large amount 176 Trace amounts separated from Yb matrix 177 The technical challenges of separating Lu are immense. Conventional separation conditions are insufficient for the effective separation of Yb / Lu, necessitating the use of more efficient methods to obtain high-purity carrier-free Lu. 177 Lu. Summary of the Invention

[0004] The purpose of this invention is to provide a multi-stage continuous separation and purification method for preparing carrier-free lutetium-177, which solves the problem of current carrier-free methods. 177 Lu cannot achieve multi-stage continuous separation, resulting in low separation efficiency.

[0005] This invention is achieved through the following technical solution:

[0006] This invention provides a method for multi-stage continuous separation and purification to prepare carrier-free lutetium-177, comprising:

[0007] After being irradiated with neutrons, it contains 177 Lu's target material 176 Yb2O3 is heated and dissolved to prepare a first nitric acid solution containing the target material;

[0008] The first nitric acid solution containing the target material was filtered and then fed onto a separation column.

[0009] The separation column was eluted with a second nitric acid solution, which has a higher acidity than the first nitric acid solution, and the reaction was detected by a nuclear detector. 177 The outflow of Lu, when detected 177 Lu flows out, and the solution is replaced with a third nitric acid solution with a higher acidity than the second nitric acid solution for continued rinsing;

[0010] After the third nitric acid solution flows out of the separation column, the effluent is loaded onto the purification column, and the effluent from the purification column is then loaded onto the conversion column.

[0011] The conversion column was eluted sequentially with a first nitric acid solution and then with a hydrochloric acid solution, and the reaction was detected by a nuclear detector. 177 The outflow of Lu, when detected 177 After Lu is desorbed to a low level, rinsing is stopped, and the first stage of separation and purification is completed.

[0012] After the hydrochloric acid solution flows out of the transfer column, the effluent is loaded onto the next separation column to begin the second stage of separation and purification, and so on, completing multiple stages of separation and purification.

[0013] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the separation column is a phosphate ester extraction resin column; the purification column is a weakly polar reverse chromatography resin column; and the conversion column is an amide resin column.

[0014] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the concentration of nitric acid in the first nitric acid solution is 0.5-1.0 mol / L; the concentration of the second nitric acid solution is 1.0-2.0 mol / L; and the concentration of the third nitric acid solution is 3.0-6.0 mol / L.

[0015] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the concentration of hydrochloric acid is 0.04-0.1 mol / L.

[0016] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, a filter with a pore size of 20-30 micrometers is used for filtration.

[0017] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the method completes at least three stages of separation and purification.

[0018] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the preparation of the first nitric acid solution containing the target material includes: [the following steps are not explicitly stated in the original text, but can be omitted:] ... 177 Lu's target material 176 Yb2O3 is dissolved by heating at 70–90 °C, evaporated to dryness, and then dissolved again with nitric acid solution to obtain the first nitric acid solution containing the target material.

[0019] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the volumes of the separation column, the conversion column, and the purification column are retained by an additional 50% to 200% beyond meeting the adsorption requirements.

[0020] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the flow rate for loading and elution of the separation column is 0.05-0.15 BV / min; the flow rate for loading and elution of the conversion column and the purification column is 0.3-0.6 BV / min.

[0021] Furthermore, in the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, the nuclear detector determines the progress of the separation process by detecting changes in the radioactivity count rate, as follows:

[0022] On the separation column, after the second nitric acid solution rinsing process begins, when the detector count rate changes from "low → high → low → high", the third nitric acid solution is switched, and the effluent path is changed from the waste tank to the next stage separation column. After the third nitric acid solution rinsing process begins, when the detector count rate changes from "high → low → slow decrease", the third nitric acid solution rinsing is stopped, and the separation process proceeds to the conversion column.

[0023] On the switching column, after the rinsing process of hydrochloric acid solution begins, when the detector count rate changes from "low → high → low → slow decrease", the hydrochloric acid solution rinsing is switched off, and the separation process proceeds to the next stage separation column.

[0024] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0025] This invention provides a multi-stage continuous separation and purification method for preparing carrier-free lutetium-177, utilizing a separation column for the separation of Yb, 177The process involves separating Lu; purifying the eluent after separation using a purification column to remove organic extractants; reducing the acidity of the eluent from high to low using a conversion column for secondary separation; and detecting the radioactivity count after each column using a radiodetector, switching the separation process based on the unique variation pattern of the radioactivity count. This invention provides a multi-stage continuous separation and purification method for preparing carrier-free lutetium-177. The process is simple and easy to operate, achieving multi-stage, continuous separation for preparing carrier-free lutetium-177 and significantly improving the recovery rate of lutetium-177. This provides a feasible and efficient method for the efficient preparation of carrier-free lutetium-177. Attached Figure Description

[0026] To more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly described below. It should be understood that the following drawings only show some embodiments of the present invention and should not be considered as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort. In the drawings:

[0027] Figure 1 This is a schematic diagram of the process for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification in Example 1 of the present invention.

[0028] Figure 2 The results show the radioactivity intensity of the eluent components in Example 1 of this invention.

[0029] The attached diagram shows the markings and corresponding component names:

[0030] R - Separation column, C - Purification column, D - Conversion column. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments and accompanying drawings. The illustrative embodiments and descriptions of this invention are for explanation only and are not intended to limit the invention. Unless otherwise specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0032] The technical solution of this invention is as follows:

[0033] A method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification includes:

[0034] Step 1: Irradiate the material with neutrons... 177 Lu's target material 176Yb2O3 is heated and dissolved to produce a first nitric acid solution containing the target material; and the high-level radioactive vapors are condensed and collected as a solution by reflux condensation and returned to the solution, which greatly reduces the level of radioactive vapor contamination of the production equipment and avoids the risk of radioactive pollution spread.

[0035] The preparation of the first nitric acid solution containing the target material includes: [details of the preparation process]. 177 Lu's target material 176 Yb2O3 is dissolved by heating at 70–90 °C, evaporated to dryness, and then dissolved again with nitric acid solution to obtain the first nitric acid solution containing the target material.

[0036] Step 2: The first nitric acid solution containing the target material is filtered and then fed onto a separation column to remove insoluble particulate matter from the solution; wherein, the nitric acid concentration in the first nitric acid solution containing the target material is 0.5-1.0 mol / L; the separation column is a phosphate ester extraction resin column; the filter pore size is 20-30 micrometers, and the filter can be a sand core, aluminum membrane, etc.

[0037] In the first nitric acid solution system containing the target material, the phosphate ester extraction resin separation column has a strong retention capacity for both ytterbium and lutetium ions, thus allowing the ytterbium and lutetium ions to be well retained in the upper part of the resin column for further separation.

[0038] Step 3: Elute the separation column with a second nitric acid solution with a higher acidity than the first nitric acid solution, and detect the solution using a nuclear detector. 177 The outflow of Lu, when detected 177 Lu flows out, and a third nitric acid solution with a higher acidity than the second nitric acid solution is used for rinsing.

[0039] The nitric acid concentration in the second nitric acid solution is 1.0-2.0 mol / L.

[0040] At this point, the concentration of the second nitric acid solution is significantly higher than that of the first nitric acid solution. Under these conditions, the retention capacity of the phosphate ester extraction resin column for ytterbium and lutetium ions is weakened, resulting in a decrease in the ytterbium and lutetium ion retention volume. Due to their larger ionic radius, ytterbium ions elute earlier than lutetium ions. When the nuclear detector detects that the radioactivity intensity in the effluent changes from low to high to low and then begins to increase again (where the change from low to high radioactivity intensity corresponds to the effluent eluent of ytterbium ions, and the detected gamma rays belong to Yb-175(t)),... 1 / 2 =4.2d) emission; from high to low corresponds to the right half of the ytterbium ion elution peak, that is, the ytterbium ion concentration begins to decrease, and the phenomenon reflected in the radioactivity detection is the decrease in the radioactivity intensity of Yb-175; the radioactivity intensity decreases and then begins to increase again indicates that the later-emitted lutetium ions begin to appear, and the radioactivity intensity is reflected in the radioactivity detection, and the detected radioactive rays belong to Lu-177).

[0041] The second nitric acid solution was switched to a third nitric acid solution for rinsing (the concentration of the third nitric acid solution was significantly higher than that of the third nitric acid solution. Under this condition, the retention capacity of the phosphate ester extraction resin column for ytterbium and lutetium ions was significantly weakened, and the retention volume of ytterbium and lutetium ions was significantly reduced. This allowed both ytterbium and lutetium ions to be desorbed in a short time, so that when ytterbium and lutetium could not be separated, they could quickly enter the second stage of separation, greatly reducing the time required for the process).

[0042] Step 4: After the third nitric acid solution flows out of the separation column, the effluent is loaded onto the purification column, and the effluent from the purification column is then loaded onto the conversion column.

[0043] The second nitric acid solution has a concentration of 1.0-2.0 mol / L; the third nitric acid solution has a concentration of 3.0-6.0 mol / L; the purification column is a weakly polar reverse chromatography resin column; and the conversion column is an amide resin column.

[0044] The third nitric acid solution is fed from the effluent of the separation column onto the purification column and the conversion column. The purification column is used to adsorb the phosphate ester extractant flowing out of the separation column, preventing it from contaminating the conversion column and causing partial failure of the conversion column.

[0045] Step 5: Elute the conversion column sequentially with first nitric acid solution and then hydrochloric acid solution, and detect the results using a nuclear detector. 177 The outflow of Lu, when detected 177 After Lu desorbs to a low level, rinsing is stopped, completing the first stage of separation and purification; the concentration of the hydrochloric acid solution is 0.04-0.1 mol / L.

[0046] Step 6: After the hydrochloric acid solution flows out of the transfer column, the effluent is loaded onto the next separation column to begin the second stage of separation and purification, and so on to complete the multi-stage separation and purification.

[0047] Among them, (1) when the nuclear detector detects that the radioactivity intensity in the third nitric acid solution effluent decreases from high to low to a flat level (corresponding to the desorption of ytterbium and lutetium ions, the radioactivity intensity decreases from high to low, and the low to flat level means that the radioactivity intensity no longer decreases significantly, indicating that the desorption of the separation column is basically completed and there is no need to continue to spend time rinsing), the third nitric acid solution rinsing is stopped, and the first nitric acid solution and hydrochloric acid solution are used to rinsing the conversion column in sequence (the first nitric acid solution is used to wash away the high concentration of nitric acid in the conversion column, and the hydrochloric acid solution is used to desorb ytterbium and lutetium ions in the conversion column), the hydrochloric acid solution effluent is loaded onto the column to the next stage of the separation column (entering the phosphate ester extraction resin column again to start the second stage of separation).

[0048] (2) When the nuclear detector detects that the radioactivity intensity in the hydrochloric acid solution changes from low to high and then back to low to a flat level (the principle is the same as the third nitric acid solution rinsing separation column in case (1)), stop the hydrochloric acid solution rinsing of the conversion column and switch the hydrochloric acid solution to the second nitric acid solution rinsing of the next stage separation column (same as the second solution rinsing separation column, the subsequent process is a repetition of the above process, and will not be repeated).

[0049] (3) When the nuclear detector detects that the radioactivity intensity in the effluent of the second nitric acid solution changes from low to high to low and then begins to rise again, the second nitric acid solution is switched to the third nitric acid solution, and the third nitric acid solution is connected to the next purification column and the next conversion column.

[0050] (4) When the nuclear detector detects that the radioactivity intensity in the third solution effluent decreases from high to low to a flat level, stop the third solution rinsing and use the first nitric acid solution and hydrochloric acid solution to rinse the next stage conversion column in sequence. The hydrochloric acid solution effluent is connected to the next stage separation column.

[0051] (5) When the nuclear detector detects that the radioactivity intensity in the hydrochloric acid solution effluent changes from low to high to low to a flat level, the hydrochloric acid solution rinsing is stopped and the second nitric acid solution rinsing is switched.

[0052] (6) When the nuclear detector detects that the radioactivity intensity in the second nitric acid solution eluent changes from low to high to low and then begins to increase, the rinsing is switched to the third nitric acid solution. The third nitric acid solution is then connected to the next purification column and the next conversion column.

[0053] (7) When the nuclear detector detects that the radioactivity intensity in the third nitric acid solution effluent changes from low to high and then back to a low to flat level, stop the third nitric acid solution rinsing and use the first nitric acid solution and hydrochloric acid solution to sequentially rinse the next stage purification column. The hydrochloric acid solution effluent is the carrier-free separated and purified solution. 177 Lu solution.

[0054] (8) Stop rinsing when the nuclear detector detects that the radioactivity intensity of the hydrochloric acid solution flowing out changes from low to high to low to a flat level.

[0055] The inventors discovered that existing methods using DGA resin as an intermediate conversion column result in a large amount of... 177 Lu product loss, and it is difficult to obtain the required purity through a single separation process. 177 Lu.

[0056] Therefore, this invention proposes to perform multi-stage continuous separation and purification to obtain high-purity carrier-free products. 177The LuCl3 solution was used in this multi-stage continuous separation process. The solution system was changed using a conversion column, and the separation and purification process was monitored by a nuclear detector to change the separation process. This achieved the effect of automated cyclic separation, reduced the impact of human operation, and reduced the radiation dose to personnel.

[0057] This invention provides a multi-stage continuous separation and purification method for preparing carrier-free lutetium-177. The method utilizes a separation column to separate Yb and 177Lu; a purification column to purify the eluent after separation, removing organic extractants; a conversion column to reduce the acidity of the eluent from high to low acidity for secondary separation; and a radioactivity detector to monitor the radioactivity count after each column, switching the separation process based on the unique variation of the radioactivity count. This method is simple, easy to operate, and achieves multi-stage continuous separation for preparing carrier-free lutetium-177, significantly improving the recovery rate of lutetium-177. It provides a feasible and efficient method for the high-efficiency preparation of carrier-free lutetium-177.

[0058] This invention provides a method for the multi-stage continuous separation and purification of carrier-free lutetium-177. By employing steam collection, it reduces the risk of radioactive vapor contamination of production equipment; by using a conversion column to achieve multi-stage continuous separation, it reduces personnel operation steps and the risk of radioactive exposure; and by using a purification column to purify the A3 effluent, it removes organic extractants, greatly reducing the risk of extractant contamination of the conversion column. 177 Lu residual loss; by detecting the radioactivity intensity of the effluent in different processes using a nuclear detector, the separation process can be accurately switched according to different detection results, thus achieving continuous separation.

[0059] In response to the existing separation process 177 When Lu is converted from a high-acidity solution to a low-acidity solution via a conversion column, there is a relatively significant [effect / effect]. 177 The problem of difficult desorption of residual Lu (approximately 10%-20%) is addressed by this invention. This invention proposes an online purification method using a weakly polar reverse-polarity chromatographic resin column for high-acidity solutions. This method removes phosphate ester organic extractants from the solution without requiring complex treatments such as high-temperature evaporation, thus avoiding contamination of the conversion column resin by phosphate ester organic extractants. 177 Lu does not leave a large amount of residue on the conversion column, improving... 177 Lu recovery rate and conversion column lifespan.

[0060] To further illustrate the present invention, the following embodiments describe the method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification provided by the present invention. However, it should be understood that these embodiments are implemented under the premise of the technical solution of the present invention, and provide detailed implementation methods and specific operating procedures. They are only for further illustrating the features and advantages of the present invention, and are not intended to limit the scope of the claims of the present invention. The scope of protection of the present invention is not limited to the following embodiments.

[0061] Example 1:

[0062] Please refer to Figure 1 The multi-stage continuous separation and purification method for preparing carrier-free lutetium-177 according to embodiments of the present invention completes three-stage continuous separation and purification, including:

[0063] (1) After being irradiated with neutrons, containing 177 Lu's target material 176 Yb2O3 is dissolved by heating to obtain a nitric acid solution with an acidity of a1, thus obtaining a solution. The target material is dissolved and evaporated using a vacuum distillation apparatus at a heating temperature of 70-90℃. After the dissolution and evaporation processes are completed, it is dissolved again with a nitric acid solution with an acidity of a1 to obtain a solution.

[0064] (2) The solution is filtered and loaded onto the resin column R1;

[0065] (3) The R1 column was then eluted with a nitric acid solution with an acidity of a2, and the solution was detected by a nuclear detector. 177 The outflow of Lu, when detected 177 After Lu flows out, the rinsing solution is replaced with a nitric acid solution with an acidity of a3 instead of a nitric acid solution with an acidity of a2.

[0066] (4) After the nitric acid solution with acidity a3 flows out from the separation column R1, it is loaded onto the purification column C1, and the effluent from the purification column C1 is then loaded onto the conversion column D1.

[0067] (5) Elute the conversion column D1 sequentially with nitric acid solution with acidity a1 and hydrochloric acid solution with acidity b1. The effluent solution from b1 is then loaded onto the separation column R2 and detected by a nuclear detector. 177 The outflow of Lu, when detected 177 After Lu is desorbed to a low level, rinsing is stopped, and the first stage of separation and purification is completed.

[0068] (6) After the separation column R2 in (5) is completed, the separation column R2 is rinsed with a nitric acid solution with an acidity of a2. The rinsing solution is replaced with a nitric acid solution with an acidity of a3 by a nuclear detector.

[0069] (7) Load the nitric acid solution with an acidity of a1 onto the purification column C2, and then load the effluent from the purification column C2 onto the conversion column D2.

[0070] (8) Elute the conversion column D2 sequentially with nitric acid solution with acidity a1 and hydrochloric acid solution with acidity b1. The effluent solution from b1 is then loaded onto the separation column R3 and detected by a nuclear detector. 177 The outflow of Lu, when detected 177 After Lu is desorbed to a low level, rinsing is stopped, and the second stage of separation and purification is completed.

[0071] (9) After the separation column R3 in (8) is completed, the separation column R3 is rinsed with a nitric acid solution with an acidity of a2. The rinsing solution is replaced with a nitric acid solution with an acidity of a3 by a nuclear detector.

[0072] (10) Load the nitric acid solution with acidity a3 onto the purification column C3, and then load the effluent from the purification column C3 onto the conversion column D3.

[0073] (11) The D3 column was sequentially eluted with nitric acid solution with acidity a1 and hydrochloric acid solution with acidity b1. The effluent from b1 was of high purity. 177 LuCl3 solution.

[0074] The acidity of the nitric acid solutions a1, a2, and a3 is 0.04-0.1, 1.0-2.0, and 4.0-6.0 mol / L, respectively; the acidity of the hydrochloric acid solution b1 is 0.04-0.1 mol / L.

[0075] The conversion column D is an amide resin column; the separation column R is a phosphate ester resin column; and the purification column C is a weakly polar reverse chromatography resin column.

[0076] The solution loading and elution flow rate for separation column R is 0.05-0.15 BV / min; the solution loading and elution flow rate for transfer column D is 0.3-0.6 BV / min; purification column C and transfer column D are connected in series and have the same flow rate.

[0077] The nuclear detector uses a detection logic that determines the progress of the separation process by detecting changes in the radioactivity count rate, achieving multi-stage continuous separation of “R1→D1→R2→D2→R3→D3→”, as detailed below:

[0078] (1) On separation columns R1, R2, and R3, after the process of rinsing with nitric acid solution of acidity a2 begins, when the detector count rate changes from "low → high → low → high", a switch is made (the nitric acid solution of acidity a2 is switched to the nitric acid solution of acidity a3), and at the same time, the effluent path is changed from the waste tank to separation columns R2 and R3; after the rinsing process of nitric acid solution of acidity a3 begins, when the detector count rate changes from "high → low → slow decrease", a switch is made (rinsing with nitric acid solution of acidity a3 is stopped), and the separation process proceeds to conversion columns D1, D2, and D3.

[0079] (2) After the rinsing process of the eluent solution with acidity of b1 hydrochloric acid solution on the conversion columns D1, D2 and D3 begins, when the detector count rate changes from "low → high → low → slow decrease", the switch is made (the rinsing of b1 hydrochloric acid solution is stopped) and the separation process proceeds to the separation columns R2 and R3.

[0080] Example 1

[0081] Enrichment with 10mg 176 Yb2O3 powder was loaded into a quartz tube, which was then fused together. The quartz tube was then loaded into an aluminum target tube and welded together to obtain the target.

[0082] After the target was prepared, it was irradiated in the reactor for 5 days. After being removed from the reactor, the aluminum target tube was cut to obtain a quartz tube, which was then crushed and poured out for enrichment. 176 Yb₂O₃ target material was dissolved by heating using a dissolution device to obtain a 0.1 mol / L nitric acid system. 176 Yb(NO3)3 solution, 177 Lu activity 102.4 mCi. The concentration of nitric acid solution with acidity a1 is 1.0 mol / L, the concentration of nitric acid solution with acidity a2 is 2.0 mol / L, the concentration of nitric acid solution with acidity a3 is 4.0 mol / L, and the concentration of hydrochloric acid b1 is 0.1 mol / L.

[0083] The solution was filtered and loaded onto the R1 separation column, and then the separation process of Example 1 was followed to obtain a carrier-free lutetium-177 solution.

[0084] The solution loading and elution flow rate for separation column R is 0.15 BV / min; the solution loading and elution flow rate for transfer column D is 0.6 BV / min. Purification column C and transfer column D are connected in series with the same flow rate.

[0085] Among them, the dimensions of columns R1, R2, and R3 are Φ20×250mm, and the dimensions of columns D1, D2, and D3 are Φ10×50mm.

[0086] The changes in radioactivity intensity in the eluent components are detected by a nuclear detection device to determine the separation process and elution / desorption status. Taking the first stage as an example of multi-stage continuous separation... Figure 2 As shown.

[0087] After the first stage of separation 175 Yb activity decreased by 95%, with subsequent decreases of 98% and 99% in the second and third stages, respectively. The separation factor was approximately 10. 5 , 177 The purity of Lu nuclei reached 99.99%, and the main indicators met the requirements for carrier-free systems. 177 Lu uses the standard.

[0088] Example 2:

[0089] Based on the results of thermal experiments: Under conditions without a purification column, the transformation process of the transformation column... 177 The Lu recovery rate is approximately 80%. This invention proposes a method for purifying the R-column eluent using a C-column to remove phosphate ester extractants. To this end, this invention conducted simulation verification experiments to validate the method:

[0090] First, the monophosphate resin column (Φ10×50 mm) was eluted with 4.0 mol / L HNO3. A certain amount of Lu was added to the effluent, and then the solution was loaded onto a purification column (Φ10×20 mm). The results are shown in Table 1.

[0091] Table 1. Changes in the content of organic extractant and Lu in the eluent after purification by the purification column.

[0092] Phosphorus content Lu content Before washing the C-pillar 9.9mg 0.1mg After washing the C-column 0.09mg 0.096mg Phosphorus removal rate / Lu recovery rate 99％ 96％

[0093] ICP-AES analysis showed that the Lu content in the desorption solution was 96%. The solution was sampled and microwave digested, then heated and evaporated before being dissolved and diluted for ion chromatography analysis. The ion chromatography analysis showed that the phosphate concentration was low, and the phosphorus removal rate obtained by combining the column buffer was over 99%.

[0094] Table 1 shows that adding a C-column (weakly polar reverse chromatography resin column) can prevent the organic extractant from entering the D-column and causing partial failure of the D-column, and can also prevent the organic extractant from entering the D-column. 177 The Lu loss rate was reduced from approximately 20% per level to approximately 4%.

[0095] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. 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 preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, characterized in that, include: After being irradiated with neutrons, it contains 177 Lu's target material 176 Yb2O3 is heated and dissolved to prepare a first nitric acid solution containing the target material; The first nitric acid solution containing the target material was filtered and then fed onto a separation column. The separation column was eluted with a second nitric acid solution, which has a higher acidity than the first nitric acid solution, and the reaction was detected by a nuclear detector. 177 The outflow of Lu, when detected 177 Lu flows out, and the solution is replaced with a third nitric acid solution with a higher acidity than the second nitric acid solution for continued rinsing; After the third nitric acid solution flows out of the separation column, the effluent is loaded onto the purification column, and the effluent from the purification column is then loaded onto the conversion column. The conversion column was eluted sequentially with a first nitric acid solution and then with a hydrochloric acid solution, and the reaction was detected by a nuclear detector. 177 The outflow of Lu, when detected 177 After Lu is desorbed to a low level, rinsing is stopped, and the first stage of separation and purification is completed. After the hydrochloric acid solution elutes from the conversion column, the effluent is fed onto the next separation column to begin the second stage of separation and purification, and so on, completing multiple stages of separation and purification. The separation column is a phosphate ester extraction resin column; the purification column is a weakly polar reverse chromatography resin column; and the conversion column is an amide resin column. The concentration of nitric acid in the first nitric acid solution is 0.5-1.0 mol / L; the concentration of the second nitric acid solution is 1.0-2.0 mol / L; and the concentration of the third nitric acid solution is 3.0-6.0 mol / L.

2. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The concentration of the hydrochloric acid is 0.04-0.1 mol / L.

3. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The filtration process uses a filter with a pore size of 20-30 micrometers.

4. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The method described herein completes at least a three-stage separation and purification process.

5. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The preparation of the first nitric acid solution containing the target material includes: [The process involves] mixing the target material with... 177 Lu's target material 176 Yb2O3 is dissolved by heating at 70~90℃, evaporated to dryness, and then dissolved again with nitric acid solution to obtain the first nitric acid solution containing the target material.

6. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The volumes of the separation column, the conversion column, and the purification column are reserved by an additional 50% to 200% beyond the adsorption requirements.

7. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The loading and elution flow rates for the separation column are both 0.05-0.15 BV / min; the loading and elution flow rates for the conversion column and the purification column are both 0.3-0.6 BV / min.

8. The method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification according to claim 1, characterized in that, The nuclear detector determines the progress of the separation process by detecting changes in the radioactivity count rate, as follows: On the separation column, after the second nitric acid solution rinsing process begins, the detector count rate changes during the "low" phase. high Low When the value is "high", switch to the third nitric acid solution and simultaneously change the effluent path from the waste tank to the next stage separation column; after the third nitric acid solution rinsing process begins, when the detector count rate changes to "high", Low When the rate of decrease is slow, switch to stop the third nitric acid solution rinsing and proceed the separation process to the conversion column; On the conversion column, after the rinsing process with hydrochloric acid solution begins, when the detector count rate changes to a "low" state... high Low When the temperature drops slowly, switch to stop the hydrochloric acid solution rinsing and proceed the separation process to the next separation column.

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