Method for preparing carrier-free lutetium-177 by means of multistage continuous separation and purification

Abstract

The present invention belongs to the field of radioactive isotope preparation. Disclosed is a method for preparing carrier-free lutetium-177 by means of multistage continuous separation and purification. The method comprises: heating and dissolving a 177Lu-containing target material 176Yb2O3 which is subjected to neutron irradiation, so as to prepare a first nitric acid solution containing the target material; after filtering said first nitric acid solution and loading same onto a separation column, using a second nitric acid solution and a third nitric acid solution to wash the separation column, and allowing an effluent to pass a purification column and then loading same onto a conversion column; and using the first nitric acid solution and a hydrochloric acid solution to wash the conversion column. The method for preparing carrier-free lutetium-177 by means of multistage continuous separation and purification provided in the present invention has simple processes, is easily operable, implements multistage continuous separation for preparation of carrier-free lutetium-177, remarkably improves the recovery rate of lutetium-177, and offers a feasible and efficient method for high-efficient preparation of carrier-free lutetium-177.

Description

A method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification Technical Field

[0001] The present invention relates to the field of radioisotope preparation, and in particular to a method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification. Background Art

[0002] 177 Lu, as a medical radioisotope, has excellent nuclear physical properties: suitable half-life (6.6 days), beta rays (average energy 149 keV) and gamma ray energy (208.4 keV, 10.4%). 177 Lu-labeled radiopharmaceuticals have become a hot topic in the field of 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 prostate cancer, with significant results.

[0003] 177 Lu can be divided into carrier 177 Lu and unsupported Lu-177, among which are used in radioligand therapy 177 Lu requires a higher specific activity, so it is mostly unsupported lutetium-177. 177 The nuclear reaction for the preparation of Lu is 176 Yb(n,γ) 177 Yb, 177 Yb decays through β- 1 / 2 =1.9h) generated 177 Lu. Since Yb / Lu are two adjacent lanthanide heavy rare earth elements, their physical and chemical properties are very similar, making separation difficult. 177 During the Lu 177 The chemical amount of Lu is generally tens of micrograms, and 176 The chemical amount of Yb is as high as several hundred milligrams to grams, and the Yb / Lu mass ratio is generally around 10 3 -10 5 It can be seen that in a radioactive environment, a large amount of 176 Separation of trace amounts of Yb in a matrix 177 The technical challenge of Lu is great. It is difficult to effectively separate Yb / Lu using conventional separation conditions. A more efficient separation method must be used to obtain high-purity carrier-free 177 Lu.

[0004] Summary of the Invention

[0005] The purpose of the present invention is to provide a method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification, which solves the current carrier-free 177Lu cannot achieve multi-stage continuous separation and has the problem of low separation efficiency.

[0006] The present invention is achieved through the following technical solutions:

[0007] The present invention provides a method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, comprising:

[0008] After neutron irradiation, 177 Lu target material 176 Yb2O3 is heated and dissolved to form a first nitric acid solution containing the target material;

[0009] The first nitric acid solution containing the target material is filtered and then loaded onto a separation column;

[0010] The separation column is washed with a second nitric acid solution having a higher acidity than the first nitric acid solution, and the separation column is detected by a nuclear detector. 177 Lu outflow, when testing 177 When Lu flows out, replace it with a third nitric acid solution with a higher acidity than the second nitric acid solution and continue eluting;

[0011] 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;

[0012] The conversion column is washed with the first nitric acid solution and the hydrochloric acid solution in sequence, and the nuclear detector is used to detect 177 Lu outflow, when testing 177 When Lu desorption reaches a lower level, elution is stopped, completing the first stage of separation and purification;

[0013] After the hydrochloric acid solution flows out of the conversion column, the effluent is transferred to the next separation column to start the second stage of separation and purification, completing the multi-stage separation and purification in sequence.

[0014] Furthermore, in the multi-stage continuous separation and purification method for preparing carrier-free lutetium-177, the separation column is a phosphate elution resin column; the purification column is a weak polarity reverse chromatography resin column; and the conversion column is an amide resin column.

[0015] Furthermore, in the multi-stage continuous separation and purification method for preparing carrier-free lutetium-177, 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.

[0016] Furthermore, in the method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, the concentration of hydrochloric acid is 0.04-0.1 mol / L.

[0017] Furthermore, in the method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, a filter with a pore size of 20-30 microns is used for filtration.

[0018] Furthermore, in the method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, the method completes at least three stages of separation and purification processes.

[0019] Furthermore, in the method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, the preparation of the first nitric acid solution containing the target material comprises: 177 Lu target material 176 Yb2O3 is heated and dissolved at 70-90°C, evaporated to dryness, and then redissolved in nitric acid solution to obtain a first nitric acid solution containing the target material.

[0020] Furthermore, in the method for preparing carrier-free lutetium-177 by 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 the volume required for adsorption.

[0021] Furthermore, in the multi-stage continuous separation and purification method for preparing carrier-free lutetium-177, the solution loading and elution flow rates of the separation column are both 0.05-0.15BV / min; the solution loading and elution flow rates of the conversion column and the purification column are both 0.3-0.6BV / min.

[0022] Furthermore, in the method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, the nuclear detector determines the progress of the separation process by detecting changes in the radioactive counting rate, as follows:

[0023] On the separation column, after the second nitric acid solution elution 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 liquid tank to the next-level separation column; after the third nitric acid solution elution process begins, when the detector count rate changes from "high → low → slowly decreasing", the third nitric acid solution elution is switched to stop, and the separation process proceeds to the conversion column;

[0024] On the conversion column, after the elution process of the hydrochloric acid solution begins, when the detector count rate changes from "low → high → low → slowly decreasing", the hydrochloric acid solution elution is stopped and the separation process proceeds to the next separation column.

[0025] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0026] The present invention provides a method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, which uses a separation column to separate Yb, 177Lu is separated; the eluent after the separation column is purified using a purification column to remove the organic extractant; the acidity of the eluent after separation is reduced from high acidity to low acidity using a conversion column for use in the second stage separation; the radioactivity count after each column is detected using a radioactivity detector, and the separation process is switched according to the unique change pattern of the radioactivity count. The method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification provided by the present invention is simple and easy to operate, realizes multi-stage and continuous separation and preparation of carrier-free lutetium-177, and significantly improves the recovery rate of lutetium-177, providing a feasible and efficient method for the efficient preparation of carrier-free lutetium-177. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the following briefly introduces the drawings required for use in the examples. It should be understood that the following drawings only illustrate certain embodiments of the present invention and should not be considered as limiting the scope. A person of ordinary skill in the art can also derive other relevant drawings based on these drawings without inventive effort. In the drawings:

[0028] FIG1 is a schematic diagram of the process of preparing carrier-free lutetium-177 by multi-stage continuous separation and purification according to Example 1 of the present invention.

[0029] FIG2 shows the radioactivity intensity results of the eluent components in Example 1 of the present invention.

[0030] Markings and corresponding parts names in the accompanying drawings:

[0031] R-separation column, C-purification column, D-conversion column. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with Examples and accompanying drawings. The illustrative embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention. In the examples, if specific conditions are not specified, the conditions according to conventional conditions or manufacturer's recommendations are used. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.

[0033] The technical solution of the present invention is:

[0034] A method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, comprising:

[0035] Step 1: After neutron irradiation, 177 Lu target material 176Yb2O3 is heated and dissolved to form the first nitric acid solution containing the target material; and the high-level radioactive steam is condensed and collected in the form of a solution through condensation reflux and returned to the dissolution liquid, which greatly reduces the level of contamination of production equipment by radioactive steam and avoids the risk of radioactive contamination spreading.

[0036] The preparation of the first nitric acid solution containing the target material comprises: 177 Lu target material 176 Yb2O3 is heated and dissolved at 70-90°C, evaporated to dryness, and then redissolved in nitric acid solution to obtain a first nitric acid solution containing the target material.

[0037] Step 2: The first nitric acid solution containing the target material is filtered and then applied to a separation column to remove insoluble particles in 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 eluting resin column; the filter pore size is 20-30 microns, and the filter can be a sand core, aluminum membrane, etc.

[0038] Among them, in the first nitric acid solution system containing the target material, the phosphate elution resin separation column has a strong retention ability for ytterbium and lutetium ions, so that the ytterbium and lutetium ions are well retained on the upper part of the resin column for the next separation.

[0039] Step 3: Use a second nitric acid solution with a higher acidity than the first nitric acid solution to elute the separation column and detect it through a nuclear detector. 177 Lu outflow, when testing 177 Lu flows out, and the third nitric acid solution with higher acidity than the second nitric acid solution is replaced to continue eluting.

[0040] Wherein, the nitric acid concentration in the second nitric acid solution is 1.0-2.0 mol / L.

[0041] At this time, the concentration of the second nitric acid solution is significantly greater than that of the first nitric acid solution. Under this condition, the retention capacity of the phosphate elution resin column for ytterbium and lutetium ions is relatively weakened, the retention volume of ytterbium and lutetium ions is reduced, and ytterbium ions flow out earlier than lutetium ions due to their larger ion radius. When the nuclear detector monitors the radioactivity intensity in the effluent from low to high to low and then begins to increase (wherein, the radioactivity intensity from low to high corresponds to the outflow of ytterbium ions, 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 begins to increase from the aforementioned decrease, indicating that the later eluting lutetium ions begin to appear at this time, and the radioactivity intensity begins to increase from the radioactivity detection, and the corresponding radioactive rays detected belong to Lu-177).

[0042] The second nitric acid solution is switched to the third nitric acid solution for elution (the concentration of the third nitric acid solution is significantly higher than that of the third nitric acid solution. Under this condition, the retention capacity of the phosphate elution resin column for ytterbium and lutetium ions is significantly weakened, and the retention volume of ytterbium and lutetium ions is significantly reduced, so that the ytterbium and lutetium ions are desorbed in a short time, so that the ytterbium and lutetium ions can quickly enter the second stage of separation when they cannot be separated, greatly reducing the time required for the process).

[0043] Step 4: After the third nitric acid solution flows out of the separation column, the effluent is loaded onto a purification column, and the effluent from the purification column is then loaded onto a conversion column;

[0044] The concentration of the second nitric acid solution is 1.0-2.0 mol / L; the concentration of the third nitric acid solution is 3.0-6.0 mol / L; the purification column is a weak polar reverse chromatography resin column; and the conversion column is an amide resin column.

[0045] The third nitric acid solution is transferred from the effluent of the separation column to the purification column and the conversion column. The purification column is used to adsorb the phosphate extractant flowing out of the separation column to prevent it from contaminating the conversion column and causing partial failure of the conversion column.

[0046] Step 5: Use the first nitric acid solution and the hydrochloric acid solution to wash the conversion column in sequence, and detect it through the nuclear detector. 177 Lu outflow, when testing 177 After Lu is desorbed to a lower level, elution is stopped to complete the first stage of separation and purification; the concentration of the hydrochloric acid solution is 0.04-0.1 mol / L.

[0047] Step 6: After the hydrochloric acid solution flows out of the conversion column, the effluent is transferred to the next separation column to start the second stage of separation and purification, completing the multi-stage separation and purification in sequence.

[0048] Among them, (1) when the nuclear detector monitors that the radioactivity intensity in the effluent of the third nitric acid solution decreases from high to low to a gentle level (corresponding to the desorption of ytterbium and lutetium ions, the radioactivity intensity decreases from high to low, and the radioactivity intensity decreases from low to a gentle level, which means that the desorption of the separation column is basically completed and there is no need to continue to spend time on elution), the elution of the third nitric acid solution is stopped, and the conversion column is sequentially eluted with the first nitric acid solution and the hydrochloric acid solution (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 the ytterbium and lutetium ions in the conversion column), and the effluent of the hydrochloric acid solution is transferred to the next-level separation column (entering the phosphate elution resin column again to start the second-level separation).

[0049] (2) When the nuclear detector detects that the radioactivity intensity in the hydrochloric acid solution changes from low to high and then to a low to a flat level (the principle is the same as that of the third nitric acid solution eluting the separation column in the description of situation (1)), the hydrochloric acid solution is stopped from eluting the conversion column, and the hydrochloric acid solution is switched to the second nitric acid solution to elute the next-level separation column (the subsequent processes are repeated in the same way as the second solution eluting the separation column, which will not be repeated).

[0050] (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 increase, 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.

[0051] (4) When the nuclear detector detects that the radioactivity intensity in the effluent of the third solution decreases from high to low and then to a flat level, the elution of the third solution is stopped, and the first nitric acid solution and the hydrochloric acid solution are used to sequentially elute the next-stage conversion column, and the effluent of the hydrochloric acid solution is connected to the next-stage separation column.

[0052] (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 elution is stopped and switched to the second nitric acid solution elution.

[0053] (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 eluent is switched to the third nitric acid solution, and the third nitric acid solution is connected to the next-stage purification column and the next-stage conversion column.

[0054] (7) When the nuclear detector detects that the radioactivity intensity in the effluent of the third nitric acid solution increases from low to high and then to a low to a flat level, the elution of the third nitric acid solution is stopped, and the first nitric acid solution and the hydrochloric acid solution are used to sequentially elute the next level of purification column. The effluent of the hydrochloric acid solution is the carrier-free solution after separation and purification. 177 Lu solution.

[0055] (8) Stop eluting when the nuclear detector detects that the radioactivity intensity of the hydrochloric acid solution effluent changes from low to high to low to a flat level.

[0056] The inventors found that the existing method of using DGA resin as an intermediate conversion column would 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.

[0057] Therefore, the present invention proposes to carry out multi-stage continuous separation and purification to obtain high-purity carrier-free 177LuCl3 solution, the multi-stage continuous separation adopts conversion column to convert the solution system, and adopts nuclear detector to monitor the separation and purification process to change the separation process, achieving the effect of automated cyclic separation, reducing the impact of human operation and reducing the exposure dose of personnel.

[0058] The present invention provides a method for preparing carrier-free lutetium-177 through multi-stage continuous separation and purification. The method utilizes a separation column to separate Yb and 177Lu; a purification column to purify the eluent after the separation column to remove the organic extractant; a conversion column to reduce the acidity of the eluent after separation from high acidity to low acidity for use in the second stage of separation; and a radioactivity detector to detect the radioactivity count after each column, switching the separation process based on the unique variation pattern of the radioactivity count. The method of the present invention is simple and easy to operate, achieves multi-stage, continuous separation and preparation of carrier-free lutetium-177, and significantly improves the recovery rate of lutetium-177, providing a feasible and efficient method for the efficient preparation of carrier-free lutetium-177.

[0059] The present invention provides a method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification. The method reduces the risk of radioactive steam contaminating production equipment and generating radioactive contamination by adopting steam collection. The method realizes multi-stage continuous separation by using a conversion column, which can reduce the number of human operation steps and the risk of radioactive exposure. The method also reduces the risk of the extractant contaminating the conversion column by adopting a purification column to purify the a3 effluent and remove the organic extractant. 177 Lu residual loss; the radioactive intensity of the effluent species in different processes is detected by nuclear detectors, and the separation process is accurately switched according to different detection results to achieve continuous separation.

[0060] For the existing separation process 177 When Lu is converted from high acidity solution to low acidity solution through the conversion column, there is a significant 177 The present invention proposes to use a weak polarity reverse chromatographic resin column to perform online purification of high acidity solution, which can remove the phosphate organic extractant in the solution without the need for complex treatment such as high temperature evaporation, thereby avoiding the contamination of the conversion column resin by the phosphate organic extractant. 177 Lu does not remain in large quantities on the conversion column, which improves 177 Lu recovery and conversion column life.

[0061] To further illustrate the present invention, the following multi-stage continuous separation and purification method for preparing carrier-free lutetium-177 provided by the present invention is described in conjunction with examples. However, it should be understood that these examples are implemented based on the technical solution of the present invention, and detailed implementation methods and specific operating procedures are provided only to further illustrate the features and advantages of the present invention, rather than to limit the claims of the present invention. The scope of protection of the present invention is not limited to the following examples.

[0062] Example 1:

[0063] Referring to FIG. 1 , the method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification according to an embodiment of the present invention completes three-stage continuous separation and purification, including:

[0064] (1) After neutron irradiation, 177 Lu target material 176 Yb2O3 is heated and dissolved into a nitric acid solution with an acidity of a1 to obtain a dissolving solution; a reduced pressure distillation device is used for the target material dissolution and evaporation process, and the heating temperature is 70-90°C. After the dissolution and evaporation process is completed, it is redissolved in a nitric acid solution with an acidity of a1 to obtain a dissolving solution;

[0065] (2) The dissolved solution is filtered and loaded onto the resin column R1;

[0066] (3) Then, the R1 column was washed with a nitric acid solution with an acidity of a2 and detected by a nuclear detector. 177 Lu outflow, when testing 177 After Lu flows out, the eluent is replaced with a nitric acid solution with acidity a2 and a nitric acid solution with acidity a3;

[0067] (4) After the nitric acid solution with acidity a3 flows out of the separation column R1, it is loaded onto the purification column C1. The effluent from the purification column C1 is then loaded onto the conversion column D1.

[0068] (5) Use nitric acid solution with acidity a1 and hydrochloric acid solution with acidity b1 to sequentially elute the conversion column D1. The solution flowing out of b1 is loaded onto the separation column R2 and detected by the nuclear detector. 177 Lu outflow, when testing 177 When Lu desorption reaches a lower level, elution is stopped, completing the first stage of separation and purification;

[0069] (6) After the separation column R2 is loaded in (5), the separation column R2 is eluted with a nitric acid solution with an acidity of a2, and the eluent is replaced with a nitric acid solution with an acidity of a3 after detection by a nuclear detector;

[0070] (7) A nitric acid solution with an acidity of a1 is loaded onto a purification column C2, and the effluent from the purification column C2 is loaded onto a conversion column D2;

[0071] (8) Use nitric acid solution with acidity a1 and hydrochloric acid solution with acidity b1 to sequentially elute the conversion column D2. The solution flowing out of b1 is loaded onto the separation column R3 and detected by the nuclear detector. 177 Lu outflow, when testing 177 After Lu desorption reaches a lower level, elution is stopped to complete the second stage of separation and purification;

[0072] (9) After the separation column R3 is loaded in (8), the separation column R3 is eluted with a nitric acid solution with an acidity of a2, and the elution solution is replaced with a nitric acid solution with an acidity of a3 after detection by a nuclear detector;

[0073] (10) The nitric acid solution with acidity a3 is loaded onto the purification column C3, and the effluent from the purification column C3 is loaded onto the conversion column D3;

[0074] (11) Use nitric acid solution with acidity a1 and hydrochloric acid solution with acidity b1 to sequentially elute the conversion D3 column, and the b1 effluent is high purity 177 LuCl3 solution.

[0075] The acidity of the nitric acid solution with acidity a1, a2 and a3 is 0.04-0.1, 1.0-2.0 and 4.0-6.0 mol / L respectively; the acidity b1 of the hydrochloric acid solution is 0.04-0.1 mol / L.

[0076] The conversion column D is an amide resin column; the separation column R is a phosphate resin column; and the purification column C is a weak polar reverse phase chromatography resin column.

[0077] The flow rate of the solution loading and elution of the separation column R is 0.05-0.15 BV / min; the flow rate of the solution loading and elution of the conversion column D is 0.3-0.6 BV / min; the purification column C and the conversion column D are connected in series and have the same flow rate.

[0078] The nuclear detector detection logic is: to judge the progress of the separation process by detecting the change of radioactive counting rate, and to achieve multi-stage continuous separation of "R1→D1→R2→D2→R3→D3→", as follows:

[0079] (1) After the nitric acid solution with acidity a2 as the eluent begins on the separation column R1, separation column R2, and separation column R3, when the detector count rate changes from "low→high→low→high", switching is performed (nitric acid solution with acidity a2 is switched to nitric acid solution with acidity a3), and at the same time, the effluent passage is changed from the waste liquid tank to the separation column R2 and separation column R3; after the elution process of the nitric acid solution with acidity a3 begins, when the detector count rate changes from "high→low→slowly decreasing", switching is performed (elution of the nitric acid solution with acidity a3 is stopped), and the separation process proceeds to the conversion column D1, conversion column D2, and conversion column D3.

[0080] (2) After the elution process of the eluent with the hydrochloric acid solution of acidity b1 begins on the conversion column D1, conversion column D2, and conversion column D3, when the detector count rate changes from "low → high → low → slowly decreasing", switching is performed (stopping the elution of the hydrochloric acid solution b1), and the separation process proceeds to the separation column R2 and separation column R3;

[0081] Example 1

[0082] Take 10mg enrichment 176 Yb2O3 powder is placed in a quartz tube, which is then sealed by melting. The quartz tube is then placed in an aluminum target tube, which is then sealed by welding to obtain a target.

[0083] After the target is prepared, it is put into the reactor for irradiation for 5 days. After leaving the reactor, the aluminum target tube is cut to obtain the quartz tube, and then the quartz tube is broken and poured out for enrichment. 176 The Yb2O3 target material is heated and dissolved by a dissolving device to obtain a 0.1 mol / L nitric acid system. 176 Yb(NO3)3 solution, 177 Lu activity is 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.

[0084] The solution was filtered and loaded onto an R1 separation column, and then the separation process was carried out according to Example 1 to obtain a carrier-free lutetium-177 solution.

[0085] The flow rate of the solution loading and elution of the separation column R is 0.15 BV / min; the flow rate of the solution loading and elution of the conversion column D is 0.6 BV / min. The purification column C and the conversion column D are connected in series and have the same flow rate.

[0086] Among them, the dimensions of R1, R2, and R3 columns are Φ20×250mm, and the dimensions of D1, D2, and D3 columns are Φ10×50mm.

[0087] The change in radioactivity intensity in the eluent components is detected by a nuclear detection device to determine the separation process and the elution and desorption conditions. The multi-stage continuous separation is shown in Figure 2, taking the first stage as an example.

[0088] After first stage separation 175 The Yb activity was reduced by 95%, and the second and third stages continued to reduce it by 98% and 99% respectively. The separation factor was about 10 5 , 177 The purity of Lu nucleus reaches 99.99%, and the main indicators meet the requirements of carrier-free 177 Lu uses standard.

[0089] Example 2:

[0090] According to the results of thermal experiments: Under the condition of no purification column, the transformation process of the transformation column 177 The Lu recovery rate is about 80%. The present invention proposes a method for purifying the R column desorption liquid using a C column to remove the phosphate extractant contained therein. To this end, the present invention carried out a simulation verification experiment of the method:

[0091] First, a phosphate resin column (Ø10 × 50 mm) was eluted with 4.0 mol / L HNO₃. A certain amount of Lu was added to the effluent, and the solution was then loaded onto a purification column (Ø10 × 20 mm). The results are shown in Table 1.

[0092] Table 1 Changes in the content of organic extractant and Lu in the eluent after purification by the purification column

[0093] ICP-AES analysis showed that the Lu content in the desorption liquid component was 96%; the solution was sampled for microwave digestion, heated for evaporation, dissolved and diluted, and then subjected to ion chromatography analysis. The ion chromatography analysis showed that the concentration of phosphate was low, and the phosphorus removal rate obtained by combining the upper column liquid was over 99%.

[0094] The results in Table 1 show that adding C column (weak polarity reverse chromatographic resin column) can prevent the organic extractant from entering D column and causing partial failure of D column. 177 The Lu loss rate is reduced from about 20% in a single stage to about 4%.

[0095] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method 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 in the scope of protection of the present invention.

Claims

1. A method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification, characterized in that: include: After neutron irradiation, 177 Lu target material 176 Yb2O3 is heated and dissolved to form a first nitric acid solution containing the target material; The first nitric acid solution containing the target material is filtered and then loaded onto a separation column; The separation column is eluted with a second nitric acid solution having a higher acidity than the first nitric acid solution, and the separation column is detected by a nuclear detector. 177 Lu outflow, when testing 177 Lu flows out, and a third nitric acid solution having a higher acidity than the second nitric acid solution is replaced to continue eluting; After the third nitric acid solution flows out from 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 is washed with the first nitric acid solution and the hydrochloric acid solution in turn, and the nuclear detector is used to detect 177 Lu outflow, when testing 177 After Lu is desorbed to a lower level, elution is stopped, completing the first stage of separation and purification; After the hydrochloric acid solution flows out of the conversion column, the effluent goes up the column to the next separation column, starting the second stage of separation and purification, and completing the multi-stage separation and purification in sequence.

2. The method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification according to claim 1, characterized in that: The separation column is a phosphate elution resin column; the purification column is a weak polar reverse chromatography resin column; and the conversion column is an amide resin column.

3. The method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification according to claim 1, characterized in that: 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.

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

5. The method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification according to claim 1, characterized in that: Filtration was performed using a filter with a pore size of 20-30 microns.

6. The method for preparing carrier-free lutetium-177 by multi-stage continuous separation and purification according to claim 1, characterized in that: The method at least completes three-stage separation and purification processes.

7. The method for preparing carrier-free lutetium-177 by 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 comprises: 177 Lu target material 176 Yb2O3 is heated and dissolved at 70-90°C, evaporated to dryness and then redissolved in a nitric acid solution to obtain a first nitric acid solution containing the target material.

8. The method for preparing carrier-free lutetium-177 by 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 additionally reserved by 50% to 200% beyond the requirements for adsorption.

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

10. The method for preparing carrier-free lutetium-177 by 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 radioactive count rate, as follows: On the separation column, after the elution process of the second nitric acid solution begins, when the detector count rate changes from "low→high→low→high", the third nitric acid solution is switched, and the effluent passage is changed from the waste liquid tank to the next-level separation column; after the elution process of the third nitric acid solution begins, when the detector count rate changes from "high→low→slowly decreasing", the third nitric acid solution elution is switched to stop, and the separation process proceeds to the conversion column; On the conversion column, after the elution process of the hydrochloric acid solution begins, when the detector count rate changes from "low → high → low → slowly decreasing", the hydrochloric acid solution elution is stopped, and the separation process proceeds to the next separation column.

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