Preparation method and apparatus for 188w- 188re generator

Abstract

The present invention relates to the technical field of radioisotope preparation, and provides a preparation method for a 188W-188Re generator, comprising the following steps: (1) target preparation: irradiating a WO3 target material; (2) tungsten-containing gel synthesis: using the irradiated WO3 target material to synthesize a tungsten-containing gel, and carrying out vacuum freeze drying to form gel particles; (3) tungsten-containing gel pretreatment: carrying out rinsing pretreatment on the synthesized tungsten-containing gel; and (4) generator assembly: transferring the treated tungsten-containing gel into a generator separation column filled with an adsorption material to assemble a 188W-188Re generator. The preparation method for the 188W-188Re generator of the present invention is simple and practical, the performance of the generator is stable, the radioactive operation is simple and convenient, the technical problems of uneven particle size, small specific surface area and low leaching efficiency of conventional gel-type generator column fillers are solved, and a high-quality sodium perrhenate [188Re] solution can be obtained.

Description

A sort of 188 W- 188 Preparation method and preparation device of Re generator Technical Field

[0001] The present invention relates to the technical field of radioisotope preparation, and in particular to a 188 W- 188 A preparation method and a preparation device of a Re generator. Background Art

[0002] 188 Re has a physical half-life of 17h, a maximum energy of 2.118Me (70.7%), 1.962MeV (26.3%), a maximum tissue range of 11mm, and 95% of its beta rays are absorbed within 4mm, causing little damage to surrounding tissues, making it suitable for internal irradiation therapy. At the same time, it also emits 0.155MeV (15.61%) of gamma rays, which can be used to study the biological distribution of nuclides, radiation doses, and pharmacokinetics. It has excellent nuclear physical and chemical properties and is an ideal integrated diagnosis and treatment radionuclide. 188 Re-labeled radiopharmaceuticals are used in the treatment of bone tumors, head and neck soft tissue tumors, radiosynovectomy of rheumatoid arthritis, and radioimmunotherapy of tumors, and have achieved significant therapeutic effects. 188 Re's research on radionuclide interventional internal irradiation of malignant tumors has also made great progress. 188 The demand for Re is also increasing.

[0003] 188 Re mainly from the mother 188 W(T 1 / 2 =69.4d) in the decay equilibrium system ( 188 W- 188 Re) Isolate the carrier-free 188 Re. Currently, all 188 W- 188 Re generators are all alumina column generators, which require high specific activity 188 W raw materials. And the reactor produces 188 W Need 186 W undergoes two (n, γ) reactions, and the intermediate 187 The half-life of W is only 24h. If a high specific activity is required for alumina columns, 188 W, which requires a high neutron flux rate in the reactor, is not yet commercially available in reactors with low neutron flux rates. 188 The production of W. Tungsten-containing gel particles have the characteristics of high tungsten content and are suitable for the preparation of low specific activity 188 W generator.

[0004] However, most of the gel-type generator column packings reported so far have problems such as uneven particle size, small specific surface area, unclear eluent, and poor stability, which leads to low elution efficiency of rhenium-188 solution and a large amount of radioactive impurities in the eluent, making it impossible to obtain high-quality rhenium-188 solution.

[0005] Summary of the Invention

[0006] The present invention is to solve the existing 188 W- 188 Re cannot obtain high-quality rhenium-188 solution. 188 W- 188 The preparation method and preparation device of Re generator are simple and practical, with stable generator performance and simple radioactive operation, which solves the technical problems of uneven particle size, small specific surface area and low elution efficiency of conventional gel-type generator column fillers, and can obtain high-quality high-rhenium [ 188 Re] sodium chloride solution.

[0007] The present invention is achieved through the following technical solutions:

[0008] The present invention provides a 188 W- 188 The preparation method of the Re generator comprises the following steps:

[0009] (1) Target preparation: irradiate the WO3 target material;

[0010] (2) Synthesis of tungsten-containing gel: Synthesize tungsten-containing gel using irradiated WO3 target material and form gel particles by vacuum freeze drying;

[0011] (3) Pretreatment of tungsten-containing gel: The synthesized tungsten-containing gel is rinsed and pretreated;

[0012] (4) Generator assembly: The treated tungsten-containing gel is transferred into the generator separation column filled with adsorption material, and assembled. 188 W- 188 Re generator.

[0013] Wherein, the WO3 target material is natural WO3 or enriched WO3.

[0014] Furthermore, step (1) is: weighing WO3 target material and placing it into a quartz target tube for welding and sealing, and the irradiation channel thermal neutron injection rate is ≥2×10 14 n·cm -2 s -1 The irradiation time is 8 to 30 days.

[0015] Furthermore, step (2) comprises: stirring and heating the irradiated WO3 target material with NaOH to dissolve it, adjusting its pH value to a range of 4 to 6, and then dripping a metal compound solution containing zirconium / titanium into it, heating it for reaction, and obtaining a tungsten-containing gel. The NaOH solution is used for dissolution, and the HCl solution is used for pH adjustment. The dripping speed is ≥60 drops / min and the solution does not flow in a linear manner.

[0016] Furthermore, the tungsten-containing gel is titanium tungstate, zirconium tungstate or ZrSiW gel, and the particle size of the tungsten-containing gel is 5 to 500 μm.

[0017] Furthermore, in step (2), the gel is filtered and washed after synthesis, wherein the filtering method includes high-speed centrifugation, filter paper filtration, suction filtration and the like.

[0018] Furthermore, in step (2), the vacuum freeze-drying conditions are: temperature ≦ -50°C, vacuum degree ≦ 10Pa, and drying time ≧ 8h.

[0019] Furthermore, in step (3), rinsing treatment refers to rinsing with deionized water, physiological saline or hydrogen peroxide solution. The number of rinsing times is ≥ 5 times, the time of each rinsing is ≥ 1 hour, and the total rinsing volume is 2 to 10 column volumes.

[0020] Furthermore, in step (4), the method of loading the tungsten-containing gel into a generator separation column with an adsorption material includes wet column filling and dry column filling; the adsorption material is a tungstate ion adsorbent, including hydrated zirconium oxide, acidic alumina, resin and other adsorption materials; the separation column used is made of high borosilicate glass, organic glass or quartz, including ordinary high borosilicate glass chromatography column, medium / high pressure special glass chromatography column, organic glass chromatography column, etc.

[0021] The present invention also provides a 188 W- 188 The preparation device of the Re generator comprises a target material dissolving device, a gel preparation device, a suction filtration washing device, a vacuum freeze drying device, a gel rinsing device and a generator separation column connected in sequence, wherein the generator separation column is installed in 188 W- 188 Re generator.

[0022] Furthermore, it also includes a waste liquid storage device, which is connected to the target material dissolving device, the gel preparing device, the suction filtration and washing device, the vacuum freeze drying device and the gel rinsing device.

[0023] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0024] 1. The present invention utilizes a reactor to irradiate WO3 and prepare a tungsten-containing gel, and assembles the obtained 188 W- 188The Re generator uses vacuum freeze-drying to process the gel to produce a gel column filling material with more uniform particle size, larger specific surface area and stable performance, thereby effectively controlling the stability of the column filler, thereby improving the stability of the generator and the extraction efficiency of the rhenium-188 solution, and improving the quality of the rhenium-188 solution.

[0025] 2. The present invention adopts the method of preparing gel filler by irradiating first and then synthesizing gel, which improves the stability of the gel. 188 W- 188 The Re generator has high elution efficiency for rhenium-188 solution, the eluent contains few radioactive impurities, and the quality of rhenium-188 solution is good.

[0026] 3. The present invention 88 W- 188 The preparation method of the Re generator is simple and practical, with stable performance and easy radioactive operation. The prepared rhenium-188 product has high elution efficiency and stable performance. 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 block diagram of the present invention 188 W- 188 Preparation flow chart of Re generator;

[0029] FIG2 is a comparison of the particles after the gel material was treated by vacuum freeze drying and oven drying, wherein the left side is vacuum freeze drying and the right side is oven drying;

[0030] FIG3 is a block diagram of the present invention 188 W- 188 Schematic diagram of the structure of the preparation device of Re generator.

[0031] The symbols and corresponding parts names in the attached figure are: 1-target material dissolution device, 2-gel preparation device, 3-filtration and washing device, 4-vacuum freeze drying device, 5-gel rinsing device, 6-generator separation column, 7- 188 W- 188 Re generator, 8-waste liquid storage device. DETAILED DESCRIPTION

[0032] In order to make the objectives, 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 drawings. The exemplary embodiments of the present invention and their descriptions are only used to explain the present invention and are not intended to limit the present invention.

[0033] Example 1

[0034] A sort of 188 W- 188 The preparation method of the Re generator comprises the following steps:

[0035] 1) Target preparation: Weigh 6 g of enriched tungsten oxide target material, place it into an aluminum target tube and seal it with welding. The thermal neutron flux rate of the irradiation channel is 2×10 14 n·cm -2 s -1 , irradiation time is 30 days.

[0036] 2) Target material dissolution: Alternately clean the target tube with 0.2M nitric acid and deionized water. Place the cleaned target tube into a ziplock bag with tweezers. Use pliers to crush the target tube. Pour the target material into a polyfluoride beaker. Add 20mL of 5M sodium hydroxide solution. Heat and stir at 80°C to dissolve until the liquid becomes clear and transparent. Cool it to room temperature and adjust the pH to 4-5.

[0037] 3) Gel preparation: Sodium tungstate solution was slowly added dropwise to titanium tetrachloride solution under constant stirring to obtain titanium tungstate gel. The pH of the gel was adjusted to 5-6, and then stirred at 90°C for 1 hour, and then precipitated for more than 12 hours to wait for the gel to separate.

[0038] 4) Filtration and washing: Remove the supernatant, add ultrapure water twice the volume of the gel and stir evenly, filter using a Büchner funnel, and continuously add ultrapure water to the Büchner funnel using a wash bottle. When the filtered liquid reaches more than 5 times the total volume of the gel, complete the filtration.

[0039] 5) Vacuum freeze drying: Transfer the culture dish containing the gel to a vacuum freeze dryer and dry it at a temperature ≤ -50°C and a vacuum degree ≤ 10 Pa for more than 24 hours.

[0040] 6) Generator assembly: Use physiological saline containing 3% hydrogen peroxide to rinse the titanium tungstate gel several times until the particles can quickly settle and the upper liquid is clear and transparent. The titanium tungstate gel after rinsing is wet loaded into the SPE chromatography column and assembled. 188 W- 188 Re generator.

[0041] The present invention performs irradiation before gel synthesis. Compared with preparing the gel first and then irradiating it, this operation effectively reduces radioactive impurities in the gel, helps to improve the stability of the gel, thereby improving the stability of the generator and the extraction efficiency of the rhenium-188 solution, and improves the quality of the rhenium-188 solution.

[0042] This example compares the two different operation sequences of irradiation followed by gel synthesis and gel preparation followed by irradiation. 188 W- 188 The results of the elution effect of the Re generator are shown in Table 1 and Table 2.

[0043] Table 1. Preparation of WO3 by irradiation and then gel synthesis 188 W- 188 The elution effect of Re generator

[0044] Table 2. Preparation of gel by first synthesizing and then irradiating 188 W- 188 The elution effect of Re generator

[0045] From Table 1 and Table 2, it can be seen that the generator prepared by irradiating WO3 first and then synthesizing the gel can extract the solution 188 Re has high activity and contains only a small amount of 188 W and 185 W, does not contain 187 W. 46 Sc and 48 Sc, the content of radioactive impurities is small, and high-quality rhenium-188 solution can be obtained; and the generator prepared by synthesizing gel first and then irradiating is used to extract the solution. 188 Re activity decreases, and 188 W. 185 W. 187 W. 46 Sc and 48 There are many impurities such as Sc, especially 188 W. 185 W. 187 W has a higher activity, making 188 The Re extraction efficiency was significantly reduced, and the quality of the rhenium-188 solution was poor.

[0046] Example 2

[0047] A sort of 188 W- 188 The preparation method of the Re generator comprises the following steps:

[0048] 1) Target preparation: Weigh 3.5 g of enriched tungsten oxide target material, place it into an aluminum target tube and seal it with welding. Irradiate the channel with a thermal neutron flux rate of 2×10 14 n·cm -2 s -1 , irradiation time is 30 days.

[0049] 2) Target material dissolution: Alternately clean the target tube with 0.2M nitric acid and deionized water. Place the cleaned target tube into a ziplock bag with tweezers. Use pliers to crush the target tube. Pour the target material into a polyfluoride beaker. Add 10mL of 5M sodium hydroxide solution. Heat and stir at 80°C to dissolve until the liquid becomes clear and transparent.

[0050] 3) Gel preparation: Sodium tungstate solution was slowly added dropwise to ZrOCl2·8H2O solution under constant stirring to obtain zirconium tungstate gel. The pH of the gel was adjusted to 7-8, and then stirred at 50°C for 30 minutes. The reaction was then allowed to precipitate for more than 12 hours and wait for the gel to separate.

[0051] 4) Filtration and washing: Remove the supernatant, add ultrapure water twice the volume of the gel and stir evenly, filter using a Büchner funnel, and continuously add ultrapure water to the Büchner funnel using a wash bottle. When the filtered liquid reaches more than 5 times the total volume of the gel, complete the filtration.

[0052] 5) Vacuum freeze drying: Transfer the culture dish containing the gel to a vacuum freeze dryer and dry it at a temperature ≤ -50°C and a vacuum degree ≤ 10 Pa for more than 24 hours.

[0053] 6) Generator assembly: rinse the zirconium tungstate gel several times with physiological saline containing 3% hydrogen peroxide, and load the rinsed zirconium tungstate gel into a separation column filled with hydrated zirconium oxide or acidic alumina by wet method. 188 W- 188 Re generator.

[0054] The present invention adopts vacuum freezing to dry the gel material, and the specific surface area of ​​the gel particles after treatment is 147.5m 2 / g, with an average particle size of 18.2nm. Compared with the drying method used in the prior art, the specific surface area of ​​the gel material in this embodiment is 36.9m 2 / g, and the average particle size is 2.8nm.

[0055] A comparison of the gel materials treated by the two drying methods is shown in Figure 2. As can be seen from Figure 2, the gel particles after vacuum freeze-drying are uniform in size and smaller in diameter, while the gel particles after oven-drying are larger and have uneven particle sizes. Therefore, the gel material prepared by the present invention has a more uniform particle size and a larger specific surface area, which is more conducive to improving the stability of the generator column filler.

[0056] The gel column prepared in this example has good elution efficiency, and the elution results are shown in Table 3.

[0057] Table 3. Elution results of gel column in Example 2

[0058] Example 3

[0059] A sort of 188 W- 188 The preparation method of the Re generator comprises the following steps:

[0060] 1) Target preparation: Weigh 3.5 g of enriched tungsten oxide target material, place it into an aluminum target tube and seal it with welding. The thermal neutron flux rate of the irradiation channel is 2×10 14 n·cm -2 s -1 , irradiation time is 30 days.

[0061] 2) Target material dissolution: Alternately clean the target tube with 0.2M nitric acid and deionized water. Place the cleaned target tube into a ziplock bag with tweezers. Use pliers to crush the target tube. Pour the target material into a polyfluoride beaker. Add 10mL of 5M sodium hydroxide solution. Heat and stir at 80°C to dissolve until the liquid becomes clear and transparent.

[0062] 3) Gel preparation: Sodium tungstate solution and sodium metasilicate solution were mixed evenly, and the mixed solution was slowly dropped into ZrOCl2·8H2O solution under constant stirring to obtain ZrSiW gel. The pH of the gel was adjusted to 7-8, and then stirred at 50°C for 30 minutes, and then precipitated for more than 12 hours to wait for the gel to stratify.

[0063] 4) Filtration and washing: Remove the supernatant, add ultrapure water twice the volume of the gel and stir evenly, filter using a Büchner funnel, and continuously add ultrapure water to the Büchner funnel using a wash bottle. When the filtered liquid reaches more than 5 times the total volume of the gel, complete the filtration.

[0064] 5) Vacuum freeze drying: Transfer the culture dish containing the gel to a vacuum freeze dryer and dry it at a temperature ≤ -50°C and a vacuum degree ≤ 10 Pa for more than 24 hours.

[0065] 6) Generator assembly: Use physiological saline containing 3% hydrogen peroxide to rinse the ZrSiW gel several times, and then wet-load the rinsed ZrSiW gel into a separation column filled with hydrated zirconium oxide or acidic alumina. 188 W- 188 Re generator.

[0066] Example 4

[0067] A sort of 188 W-188 The preparation device of the Re generator includes a target material dissolving device 1, a gel preparation device 2, a suction filtration and washing device 3, a vacuum freeze drying device 4, a gel rinsing device 5, a generator separation column 6 and a waste liquid storage device 8 connected in sequence. The generator separation column 6 is installed in 188 W- 188 In the Re generator 7 , the waste liquid storage device 8 is connected to the target material dissolving device 1 , the gel preparing device 2 , the suction filtration and washing device 3 , the vacuum freeze drying device 4 and the gel rinsing device 5 .

[0068] Among them, the target material dissolving device 1 is used to temporarily store, clean, crush and dissolve the irradiated tungsten-containing target material, the gel preparation device 2 is used to generate a tungsten-containing gel aqueous solution with the irradiated tungsten-containing target material and the metal compound, the suction filtration washing device 3 is used to remove most of the water in the tungsten-containing gel aqueous solution and remove salt ions in the gel, the vacuum freeze drying device 4 is used to freeze and vacuum dry to remove the remaining water in the tungsten-containing compound, the generator separation column 5 is filled with adsorption material, and the treated and dried target material is transferred to the generator separation column 5 to be assembled to form 188 W- 188 Re generator 6, the 188 W- 188 Re generator 6 is used to elute high rhenium [ 188 Re] sodium hydroxide solution, and the waste liquid storage device is used to collect the waste liquid generated by each device.

[0069] In this embodiment, the use process of the preparation device is as follows: in a shielded working box, after dissolving the target material using the target material dissolving device 1, the solution is transferred to the gel preparation device 2, and then the constant temperature metal compound solution is added thereto for mixing. Then, the gel aqueous solution is transferred to the filtration washing device 3 by a pump for filtration to remove most of the water. The gel solution is then transferred to a culture dish, and frozen and vacuum dried in a vacuum freeze drying device 4 to remove the remaining water in the gel aqueous solution. After the gel is completely dried, the gel is loaded into a column using a generator separation column 5 to assemble. 188 W- 188 Re generator 6, and finally rinse the tungsten-rhenium generator with physiological saline to obtain high-quality rhenium-188 solution.

[0070] Example 5

[0071] Use the generator of the present invention: After the column has been loaded for 48 hours, it is rinsed. Prepare 10 labeled 5 mL centrifuge tubes and place them sequentially in the sample tube rack below the outlet. Add 10 mL of normal saline to the syringe above the column. Turn on the switch below to collect 10 mL of eluent in sequence. Record the elution time to complete the elution. The elution method can be negative pressure elution, peristaltic pump, etc., which is not limited by the present invention.

[0072] 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 188 W- 188 The preparation method of Re generator is characterized in that: The following steps are involved: (1) Target preparation: irradiate the WO3 target material; (2) Synthesis of tungsten-containing gel: Synthesize tungsten-containing gel using irradiated WO3 target material, and form gel particles by vacuum freeze drying; (3) Pretreatment of tungsten-containing gel: The synthesized tungsten-containing gel is pretreated by rinsing; (4) Generator assembly: The pretreated tungsten-containing gel is transferred into the generator separation column containing the adsorption material. 188 W- 188 Re generator.

2. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: Step (1) is: weigh the WO3 target material and put it into the quartz target tube for welding and sealing. The thermal neutron injection rate of the irradiation channel is ≥2×10 14 n cm -2 s -1 The irradiation time is 8 to 30 days.

3. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: Step (2) is: stirring and heating the irradiated WO3 target material with NaOH to dissolve it, adjusting its pH value to 4-6, then dripping a metal compound solution containing zirconium / titanium, heating and reacting to obtain a tungsten-containing gel.

4. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: The tungsten-containing gel is titanium tungstate, zirconium tungstate or ZrSiW gel, and the particle size of the tungsten-containing gel is 5 to 500 μm.

5. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: In step (2), the gel needs to be filtered and washed after synthesis.

6. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: In step (2), the vacuum freeze-drying conditions are: temperature ≦-50°C, vacuum degree ≦10Pa, and drying time ≧8h.

7. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: In step (3), the rinsing treatment refers to rinsing with deionized water, saline or hydrogen peroxide solution.

8. A method according to claim 1 188 W- 188 The preparation method of Re generator is characterized in that: In step (4), the method of loading the tungsten-containing gel into a generator separation column with an adsorption material includes wet column filling and dry column filling; the adsorption material is a tungstate ion adsorbent including hydrated zirconium oxide, acidic alumina, and resin.

9. A 188 W- 188 The preparation device of Re generator is characterized in that: The invention comprises a target material dissolving device (1), a gel preparing device (2), a suction filtering and washing device (3), a vacuum freeze drying device (4), a gel rinsing device (5) and a generator separation column (6) which are connected in sequence. The generator separation column (6) is installed in 188 W- 188 Re generator (7).

10. A method according to claim 9 188 W- 188 The preparation device of Re generator is characterized in that: It also includes a waste liquid storage device (8), which is connected to the target material dissolving device (1), the gel preparing device (2), the suction filtration and washing device (3), the vacuum freeze drying device (4) and the gel rinsing device (5).

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