Adsorbent for germanium [68Ge] gallium [68Ga] generator, preparation method thereof and germanium [68Ge] gallium [68Ga] generator

Abstract

The invention discloses an adsorbent for a germanium [68Ge] gallium [68Ga] generator, a preparation method of the adsorbent and the germanium [68Ge] gallium [68Ga] generator. The adsorbent is used for adsorbing the < 68 > Ge element; the adsorbent comprises a plurality of titanium dioxide particles, wherein the specific surface area of the plurality of titanium dioxide particles is 30 m < 2 > / g to 100 m < 2 > / g; the titanium dioxide particles are composed of a plurality of nanoparticles, and the average particle size of the plurality of nanoparticles is 10 nm to 100 nm; the nanoparticles comprise mesopores, and the pore diameter of the mesopores is 5 nm to 30 nm.

Description

For germanium[ 68 Ge]gallium[ 68 Ga] generator adsorbent and preparation method thereof and germanium [ 68 Ge]gallium[ 68 Ga generator

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the right to the patent filed on September 13, 2023 entitled "A Germanium 68 Ge]gallium[ 68 The priority of Chinese patent application No. 202311178638.X entitled “A method for generating germanium [Ga] generator” and the priority of Chinese patent application No. 202311178638.X entitled “A method for generating germanium [Ga] generator” filed on September 13, 2023 68 Ge]gallium[ 68 The entire contents of the above two application documents are incorporated herein by reference. Technical Field

[0003] The present application belongs to the technical field of adsorbents, specifically to a method for the adsorption of germanium. 68 Ge]gallium[ 68 Ga] generator adsorbent and preparation method thereof and germanium [ 68 Ge]gallium[ 68 Ga] generator. Background Art

[0004] germanium[ 68 Ge]gallium[ 68 Ga] generator ( 68 Ge- 68 Ga generator) is a kind of radioactive decay and radionuclide separation principle, which converts radioactive 68 Ge source is transformed into 68 Ga, used to provide 68 Ga device. In providing 68 How to reduce the 68 Ge content and increase 68 The yield of Ga is germanium[ 68 Ge]gallium[ 68 Ga] generator improvement direction.

[0005] Generally speaking, 68 Ge- 68 Adsorption commonly used in Ga generators 68The main adsorption materials for Ge include tin dioxide, titanium dioxide, aluminum oxide, polymer matrix (such as polystyrene, polymethacrylate, etc.), silicon dioxide-organic resin copolymer, etc., but each of these adsorption materials has certain limitations.

[0006] In 1996, the Russian Cyclotron Corporation first supplied the market with modified TiO2 materials. 68 Ge- 68 Ga generator, initial elution efficiency is 60%-75%, 68 The Ge leakage rate is about 0.001% (Journal of Nuclear Medicine and Molecular Imaging, 2019, 9, 30-66); in recent years, Germany's Eckert & Ziegler and Belgium's IRE EliT have also developed commercial TiO2-based materials. 68 Ge- 68 Ga generator, but its elution efficiency gradually decreases with the increase of use time, even as low as 55% or less; US Patent US10357758B2 also discloses a method for preparing a chromatographic adsorption material for a nuclide generator, using this material to prepare a 33mCi-grade 68 Ge- 68 Ga generator, which is for 68 The initial elution efficiency of Ga is about 75%, and the elution efficiency after multiple elutions can be stabilized at more than 65%. 68 The Ge leakage rate can meet the requirements of the European Pharmacopoeia gallium chloride [ 68 Ga] solution standard (≤0.001%).

[0007] It can be seen that the prior art 68 Ge- 68 Ga generator for 68 The elution efficiency of Ga is generally not higher than 75%, because the pharmaceutical grade 68 Ge- 68 The Ga generator must meet a minimum of ≤0.001% 68 Ge leakage rate, and improve 68 The elution efficiency of Ga is often accompanied by 68 The leakage rate of Ge increases accordingly, resulting in 68 The elution efficiency of Ga is limited.

[0008] Based on the above analysis, this field still needs a method with lower 68 Ge leakage rate and higher and more stable 68 Ga elution efficiency 68 Ge- 68 Ga generator.

[0009] Summary of the Invention

[0010] The purpose of this application is to provide a method for 68 Ge]gallium[ 68 Ga] generator adsorbent and preparation method thereof can be used to take into account the adsorption 68 While the Ge element has an effect, 68 Ge]gallium[ 68 The adsorbent can be better released when eluting it in the Ga] generator 68 Ga, reduce 68 The residual Ga element in the titanium dioxide particles improves the elution efficiency. The present application also provides a germanium [ 68 Ge]gallium[ 68 Ga] generator.

[0011] In the first aspect, the embodiment of the present application provides a method for germanium [ 68 Ge]gallium[ 68 Ga] generator, the adsorbent is used to adsorb 68 Ge element; the adsorbent includes: a plurality of titanium dioxide particles; the titanium dioxide particles are composed of a plurality of nanoparticles, the average particle size of the plurality of nanoparticles is 10nm to 100nm; the titanium dioxide particles also include mesopores, the pore size of the mesopores is 5nm to 30nm.

[0012] In some optional embodiments, the specific surface area of ​​the adsorbent is 30m 2 / g to 100m 2 In some optional embodiments, the specific surface area of ​​the adsorbent is 31m 2 / g to 97m 2 / g; the average particle size of the plurality of nanoparticles is 12nm to 96nm; the pore size of the mesopores is 5.7nm to 19nm.

[0013] In some optional embodiments, the crystal phase type of the adsorbent is anatase.

[0014] In some optional embodiments, the average particle size of the adsorbent is 10 μm to 300 μm.

[0015] In some optional embodiments, the pore volume of the adsorbent is 0.1 cm 3 / g to 0.5cm 3 / g.

[0016] In some optional embodiments, the adsorbent includes: one or more of the titanium dioxide particles having an average particle size of 30-60 μm, the titanium dioxide particles having an average particle size of 50-100 μm, the titanium dioxide particles having an average particle size of 75-150 μm, and the titanium dioxide particles having an average particle size of 90-180 μm.

[0017] In some optional embodiments, the titanium dioxide particles are treated by any one or more methods of oscillation, vortexing, and ultrasound to make the surface of the titanium dioxide particles smooth.

[0018] In the second aspect, the embodiment of the present application is a method for 68 Ge- 68 A method for preparing a titanium dioxide adsorbent for a Ga generator, wherein the adsorbent is prepared by a sol-gel method, comprising the following steps:

[0019] Dissolving the titanium source in an organic alcohol and then adding glacial acetic acid to obtain a titanium source solution;

[0020] adding the titanium source solution dropwise into the purified aqueous solution while stirring, and allowing to stand to obtain a first gel; heating and retaining the first gel, and recrystallizing the first gel to obtain a second gel;

[0021] After the second gel is formed by the first calcination, solid particles with a particle size of 10-300 μm are ground and screened for surface modification, and then the second calcination is performed to obtain an adsorbent.

[0022] In some optional embodiments, the stirring speed of the dropwise addition while stirring is 10-100 rpm, and the dropwise addition rate is 1-100 mL / min.

[0023] In some optional embodiments, the volume ratio of the titanium source solution to purified water is 1:(0.5-10).

[0024] In some optional embodiments, the heating and insulation temperature is 110-180° C., and the time is 6-36 hours.

[0025] In some optional embodiments, the surface of the solid particles is modified by ultrasonic treatment, wherein the ultrasonic power is 50-1000 W and the time is 0.5-12 h.

[0026] In some optional embodiments, the second gel is formed by a first calcination, and then the solid particles with a particle size of 10-300 μm are crushed and screened for surface modification, and then the adsorbent is obtained by a second calcination, including: after the second gel is formed by a first calcination, the solid particles with a particle size of 30-60 μm, 50-100 μm, 75-150 μm, and 90-180 μm are crushed and screened, and then the adsorbent is obtained by a second calcination.

[0027] In some optional embodiments, the first calcination temperature is 300-700°C, and the second calcination temperature is 400-700°C.

[0028] In some optional embodiments, the first roasting time is 1-12 hours, and the second roasting time is 1-6 hours.

[0029] In the third aspect, the present application embodiment provides a germanium [ 68 Ge]gallium[ 68 Ga] generator, comprising:

[0030] The filler cylinder is filled with the adsorbent described in the first aspect or the adsorbent prepared by the preparation method described in the second aspect, and the adsorbent adsorbs 68 Ge element;

[0031] In some optional embodiments, the filler tube is made of one or more of a plastic chromatography column, a glass tube, and a quartz tube.

[0032] The present invention has the following beneficial effects:

[0033] 1) In the embodiment of the present application, the adsorbent is a titanium dioxide particle material, wherein any titanium dioxide particle is composed of a plurality of nanoparticles bonded to each other, and when the pore size of the nanoparticles is 5nm to 30nm, on the one hand, the titanium dioxide particles can have a relatively large and appropriate specific surface area, thereby improving the adsorption of the titanium dioxide particles. 68 On the other hand, the titanium dioxide particles have a suitable pore volume or adsorption site, so that they can accommodate a large amount of Ge. 68 Ge element molecules or ions can be better adsorbed 68 Ge element, while during elution, can be better released 68 Ga, reduced 68 The residual Ga element in the titanium dioxide particles improves the elution efficiency.

[0034] 2) Multiple nanoparticles are independent small particles during the preparation process, and have a certain mechanical strength. Multiple nanoparticles can stably exist in the acid leaching environment; avoiding the edge embrittlement of the titanium dioxide particles formed as a whole in the related art. The composition of multiple nanoparticles combined with each other makes the titanium dioxide particles have good structural stability and reduces the damage caused by the edge embrittlement of the titanium dioxide particles. 68 The risk of Ge element leakage is reduced, which reduces the leakage rate.

[0035] 3) The present invention adopts an improved sol-gel method to prepare titanium dioxide adsorbent. On the one hand, the process is simple, environmentally friendly, has no risk of introducing other metal ions, is efficient and convenient to prepare, and can be produced on a large scale. On the other hand, it overcomes the problem that the titanium dioxide prepared by the sol-gel method in the prior art is nanometer-sized and cannot be used as an adsorbent for a germanium-gallium generator. The titanium dioxide particles prepared by the sol-gel method are micrometer-sized and have excellent performance when used as an adsorbent for a germanium-gallium generator.

[0036] 4) The adsorbent prepared by the present invention, i.e., titanium dioxide particles, is composed of 10-100 nm nanoparticles and has a specific surface area of ​​30-100 m 2 / g, pore size is 5-30nm, and the surface is smooth, which is used as an adsorbent for 68 Ge- 68 Ga generator, significantly improved 68 Ge- 68 The performance of Ga generators, especially for the activity range above 30mCi, 68 The Ge leakage rate is reduced to about 0.0001%. 68 The Ga elution efficiency is increased to over 75%, and can be maintained above 70% for multiple elutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] To more clearly illustrate the technical solutions of the embodiments of the present application, the following briefly introduces the drawings required for use in the embodiments of the present application. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on the drawings without inventive effort.

[0038] FIG1 shows an X-ray diffraction pattern of the modified TiO2 granular material according to an embodiment of the present application;

[0039] FIG2 shows a scanning electron microscope (SEM) image of the modified TiO2 particle material of an embodiment of the present application;

[0040] FIG3 shows a scanning electron microscope (SEM) image of the modified TiO2 particle material of an embodiment of the present application;

[0041] FIG4 shows a scanning electron microscope (SEM) image of the modified TiO2 particle material of an embodiment of the present application;

[0042] FIG5 shows a 50mCi 68 Ge- 68 The elution efficiency change and linear fitting diagram of Ga generator over 200 days;

[0043] FIG6 shows an example of an 85mCi 68 Ge- 68 Long-term elution efficiency change of Ga generator.

[0044] In the accompanying drawings, the drawings are not necessarily drawn to scale. DETAILED DESCRIPTION

[0045] Hereinafter, the invention will be described in detail with reference to the accompanying drawings. 68 Ge]gallium[ 68 Ga] generator adsorbent and preparation method thereof and germanium [ 68 Ge]gallium[ 68

[0014] Embodiments of a Ga generator. However, unnecessary detailed descriptions may be omitted. For example, detailed descriptions of well-known matters and repeated descriptions of substantially identical structures may be omitted. This is to avoid unnecessary redundancy in the following description and to facilitate understanding by those skilled in the art. Furthermore, the drawings and the following description are provided to enable those skilled in the art to fully understand the present application and are not intended to limit the subject matter described in the claims.

[0046] " range " disclosed in the present application is limited in the form of lower limit and upper limit, and given range is limited by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundary of special range. The scope limited in this way can be to include end value or not include end value, and can be arbitrarily combined, that is, any lower limit can form a range with any upper limit combination. For example, if the scope of 60-120 and 80-110 is listed for specific parameters, it is understood that the scope of 60-110 and 80-120 is also expected. In addition, if the minimum range value 1 and 2 are listed, and if the maximum range value 3,4 and 5 are listed, then the following range can all be expected: 1-3, 1-4, 1-5, 2-3, 2-4 and 2-5. In this application, unless otherwise specified, the numerical range " ab " represents the abbreviation of any real number combination between a and b, wherein a and b are all real numbers. For example, a numerical range of "0-5" indicates that all real numbers between "0-5" are listed herein, and "0-5" is simply an abbreviation for these numerical combinations. Furthermore, when a parameter is expressed as an integer ≥ 2, this is equivalent to disclosing that the parameter is, for example, an integer of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0047] Unless otherwise specified, all embodiments and optional embodiments of the present application can be combined with each other to form new technical solutions, and such technical solutions should be considered to be included in the disclosure of the present application.

[0048] Unless otherwise specified, all technical features and optional technical features of this application can be combined with each other to form new technical solutions, and such technical solutions should be deemed to be included in the disclosure of this application.

[0049] Unless otherwise specified, all steps of the present application may be performed sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or may include steps (b) and (a) performed sequentially. For example, the method may further include step (c), indicating that step (c) may be added to the method in any order, for example, the method may include steps (a), (b) and (c), or may include steps (a), (c) and (b), or may include steps (c), (a) and (b), etc.

[0050] The term "multiple" as used in this application refers to more than two (including two). The term "multiple" or "several" as used in this application refers to more than two (including two). The term "multiple" or "several" as used in this application refers to more than two (including two).

[0051] The term "elution efficiency" refers to the 68 Ge decays into daughter nuclides 68 After Ga, the collected 68 The ratio of the actual amount of Ga to the theoretical amount.

[0052] The term "leakage rate" refers to the rate at which the 68 The leakage rate of Ge in the liquid 68 Activity of Ge / 68 The activity of Ga.

[0053] The term "specific surface area" refers to the total surface area per unit mass of an adsorbent material and can be measured by gas adsorption.

[0054] The term "titanium dioxide particle size" refers to the size or diameter of titanium dioxide particles, which can be measured using a laser particle size analyzer. It is understood that titanium dioxide micron particles are aggregated from nanoparticles.

[0055] The term "nanoparticles" refers to nano-sized titanium dioxide particles that aggregate to form titanium dioxide micron particles.

[0056] The term "pore size" refers to the diameter or width of a pore, a measure of pore size. It can be measured using instruments such as surface area and porosity analyzers. For example, the size of the pores within micron-sized titanium dioxide (micron-sized titanium dioxide is formed by aggregations of nano-sized titanium dioxide particles, and the pore size is the size of the pores between and within the nano-sized titanium dioxide particles).

[0057] In the first aspect, the embodiment of the present application provides a method for germanium [ 68 Ge]gallium[ 68 Ga] generator, the adsorbent is used to adsorb 68 Ge element; the adsorbent includes: a plurality of titanium dioxide particles, the titanium dioxide particles are composed of a plurality of nanoparticles, the average particle size of the plurality of nanoparticles is 10nm to 100nm; the nanoparticles include mesopores, the pore size of the mesopores is 5nm to 30nm.

[0058] The pore diameter of the mesopores may be any value among 5 nm, 10 nm, 15 nm, 20 nm, 25 nm, and 30 nm, or a range thereof.

[0059] In the embodiment of the present application, the adsorbent is a titanium dioxide particle material, wherein any titanium dioxide particle is formed by a plurality of nanoparticles bonded to each other. The plurality of nanoparticles are independent small particles during the preparation process and have a certain mechanical strength. The plurality of nanoparticles can stably exist in an acid leaching environment. This avoids the edge embrittlement of the titanium dioxide particles formed as a whole in the related art. The composition of the plurality of nanoparticles bonded to each other gives the titanium dioxide particles good structural stability and reduces the side embrittlement of the titanium dioxide particles. 68 Risk of Ge element leakage.

[0060] When the average diameter of the nanoparticles is too small, during the preparation of titanium dioxide particles, the nanoparticles with too small a particle size are relatively soft and have a small internal pore size, and are easily tightly agglomerated with multiple other nanoparticles, making it difficult to obtain titanium dioxide particles with a certain specific surface area and a suitable pore size; and when the average particle size of the nanoparticles is too large, during the preparation and use of the titanium dioxide particles, the nanoparticles with too large a particle size are easily deformed or even broken, and their cohesive strength is relatively low, making it difficult to form titanium dioxide particles with a certain mechanical strength and a suitable specific surface area. Therefore, the average particle size of the nanoparticles in the titanium dioxide particles is 10nm to 100nm; the size of the nanoparticles can be 10nm, 20nm, 50nm, 60nm, 80nm, 100nm, or in the range of 10-30, 20-60nm, 50-100nm; the pore size can be 5nm, 10nm, 15nm, 20nm, 30nm, or in the range of 5-10nm, 10-25nm, 20-30nm. In some optional embodiments, the average particle size of the plurality of nanoparticles is 50 nm to 80 nm.

[0061] It should be noted that, unless otherwise specified, the average particle size of the nanoparticles in the titanium dioxide particles in this application refers to: when the prepared titanium dioxide particles are observed by scanning electron microscopy (SEM), 200 nanoparticles are taken for statistical analysis and the average particle size of the nanoparticles is calculated.

[0062] The research found that titanium dioxide particles composed of nanoparticles are suitable for the application of germanium[ 68 Ge]gallium[ 68 When the pore size of the nanoparticles is 5nm to 30nm, on the one hand, the titanium dioxide particles can have a relatively large and appropriate specific surface area, which can improve the 68 On the other hand, the titanium dioxide particles have a higher pore volume or adsorption site, which enables them to accommodate a large amount of Ge. 68 Ge element molecules or ions can be better adsorbed 68 Ge element, while during elution, can be better released 68 Ga, reduced 68 The residual Ga element in the titanium dioxide particles improves the elution efficiency.

[0063] In some optional embodiments, the specific surface area of ​​the plurality of titanium dioxide particles is 30 m 2 / g to 100m 2 / g.

[0064] For example, the specific surface area can be 30m 2 / g, 40m 2 / g、70m 2 / g、85m2 / g、100m 2 / g, or 30-50m 2 / g, 50-100m 2 / g, 80-100m 2 / g specific surface area range.

[0065] In the embodiment of the present application, the specific surface area of ​​the titanium dioxide particles is within the above range, which can better adsorb 68 Ge element.

[0066] In some optional embodiments, the specific surface area of ​​the adsorbent is 31m 2 / g to 97m 2 / g; the average particle size of the plurality of nanoparticles is 12nm to 96nm; the pore size of the mesopores is 5.7nm to 19nm. Therefore, the above-mentioned adsorbent can further improve the elution efficiency and reduce the leakage rate.

[0067] In some optional embodiments, the crystal phase type of the adsorbent is anatase. In the embodiment of the present application, anatase titanium dioxide particles have a relatively large and more suitable specific surface area and a better pore structure, which improves the adsorption of 68 The adsorption of Ge and 68 Ga release effect.

[0068] In some optional embodiments, the average particle size of the adsorbent is 10 μm to 300 μm.

[0069] It can be understood that the adsorbent particle size described in the present application is 10-300 μm, which means that the titanium dioxide particles with a particle size range of 10-300 μm can be specific particle sizes, such as 10 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, or any range of particle size within 10-300 μm, for example, 10-50 μm, 30-60 μm, 50-150 μm, 20-200 μm, 130-260 μm, 200-300 μm; preferably, the particle size range is 30-60 μm, 50-100 μm, 75-150 μm, 90-180 μm.

[0070] In this embodiment, 10-300 μm granular titanium dioxide can reduce 68 The leakage rate.

[0071] In some optional embodiments, the pore volume of the adsorbent is 0.1 cm 3 / g to 0.5cm 3 / g.

[0072] Optionally, the pore volume of the titanium dioxide particles can be 0.1 cm 3 / g, 0.2cm 3 / g, 0.3cm 3 / g, 0.4cm 3 / g, 0.5cm 3 Therefore, the pore volume of multiple titanium dioxide particles is within the above range, which is conducive to providing sufficient sites and 68 Ge element combines, during the elution process, 68 Even if the Ge element is washed out, the titanium dioxide particles can provide enough sites to re-establish the 68 The pore volume of the plurality of titanium dioxide particles is within the above range, which facilitates the use of the appropriate elution conditions in multiple regions during elution. 68 Ga element release, improve 68 The yield of Ga can be improved, thereby improving the elution efficiency.

[0073] In some optional embodiments, the adsorbent includes one or more of the titanium dioxide particles having an average particle size of 30-60 μm, the titanium dioxide particles having an average particle size of 50-100 μm, the titanium dioxide particles having an average particle size of 75-150 μm, and the titanium dioxide particles having an average particle size of 90-180 μm. 68 Ge- 68 Ga generator elution efficiency and reduction [ 68 Ge] leakage phenomenon.

[0074] In some optional embodiments, the titanium dioxide particles are treated by any one or more methods of oscillation, vortexing, and ultrasound to make the surface of the titanium dioxide particles smooth. Any combination of oscillation, vortexing, ultrasound, etc. or any single treatment method can further make the surface of the titanium dioxide particles smooth, that is, the particles are generally smoother and have fewer sharp edges. Generally speaking, the sharp edges of the titanium dioxide particles contain a certain amount of 68 Ge, during the leaching process of the adsorbent, the sharp edges are broken and washed out, thus making the surface of the titanium dioxide particles smooth and conducive to reducing 68 Ge leakage phenomenon and improvement 68 Ge- 68 Ga generator elution efficiency.

[0075] In the second aspect, the embodiment of the present application is a method for 68 Ge- 68 A method for preparing a titanium dioxide adsorbent for a Ga generator, wherein the adsorbent is prepared by a sol-gel method, comprising the following steps:

[0076] Dissolving the titanium source in an organic alcohol and then adding glacial acetic acid to obtain a titanium source solution;

[0077] adding the titanium source solution dropwise into the purified aqueous solution while stirring, and allowing to stand to obtain a first gel; heating and retaining the first gel, and recrystallizing the first gel to obtain a second gel;

[0078] After the second gel is formed by the first calcination, solid particles with a particle size of 10-300 μm are ground and screened for surface modification, and then the second calcination is performed to obtain an adsorbent.

[0079] In this embodiment, the preparation method of titanium dioxide is a sol-gel method, which includes the following steps: dissolving a titanium source in an organic alcohol and then adding glacial acetic acid to obtain a titanium source solution; adding the titanium source solution dropwise into a purified aqueous solution while stirring, and letting it stand to obtain a first gel; heating and heat-insulating the first gel and recrystallizing it to obtain a second gel; after the second gel is formed by a first calcination, grinding and screening solid particles with a particle size of 10-300 μm for surface modification, and then subjecting it to a second calcination to obtain an adsorbent.

[0080] In the embodiment of the present application, the second gel can be understood as a gel that is slowly concentrated and recrystallized under heating conditions, and finally a large amount of solvent is removed to form a dry gel, that is, crystalline particles.

[0081] In this embodiment, the specific preparation method of the titanium source solution is a conventional sol-gel method, that is, the titanium source (for example, tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate, etc.) is dissolved in an organic alcohol solution, and then an inhibitor (for example, glacial acetic acid, etc.) is added to inhibit its hydrolysis to form a titanium source solution; this application does not make any special limitations and only provides a preferred embodiment.

[0082] In some optional embodiments, the titanium source solution is prepared by:

[0083] S1. Dissolve a titanium source (e.g., tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate, tetrahexyl titanate, etc.) in a C2-C5 alcohol solution and mix well to obtain a clear and transparent solution. The purpose of this step is to dissolve the titanium source. The volume ratio of the titanium source to the C2-C5 alcohol solution is preferably 2: (0.5-20), the titanium source is more preferably tetraisopropyl titanate or tetrabutyl titanate, the alcohol solution is more preferably isopropyl alcohol, and when the alcohol solution is isopropyl alcohol, the volume ratio of the titanium source to isopropyl alcohol is more preferably 1: (3-6).

[0084] S2. The resulting clear, transparent solution is added dropwise to glacial acetic acid while stirring to obtain a white, turbid solution. The solution is allowed to stand for a period of time until a clear, transparent solution is obtained, which is the titanium source solution. This step is intended to inhibit hydrolysis of the titanium source. The volume ratio of the titanium source to the glacial acetic acid is preferably 1:(0.5-10), more preferably 1:1.

[0085] The existing technology generally adopts sulfuric acid method, chlorination method, etc. to prepare titanium dioxide, which is complex, energy-intensive, and wasteful. The obtained titanium dioxide has high metal impurity content and complex crystal form, and cannot be used as 68 Ge- 68 Ga generator adsorption filler; US10357758B2 disclosed for 68 Ge- 68 The initial adsorption efficiency of titanium dioxide in the Ga generator adsorption filler is 75%, and the elution efficiency of long-term elution is stable at about 65%. At the same time, according to the data disclosed in the prior art, when the 68 The leakage rate of Ge is in accordance with the European Pharmacopoeia for gallium chloride [ 68 Ga] solution standard (≤0.001%), 68 The elution efficiency of Ga is generally not higher than 75%, and after multiple elutions, the elution efficiency will be significantly reduced. The sol-gel preparation method is simple, fast, environmentally friendly, and has no risk of introducing other metal ions. Therefore, it has gradually become the focus of attention of technicians. However, the titanium dioxide prepared by the existing sol-gel method is generally nano-scale. This is because after the titanium source is reacted with organic alcohol and inhibitors to form a titanium source solution, it aggregates in purified water to form sol particles of about 1 nm. Although the sol particles further grow to form a gel during the standing process, the gel is only a overlap between the sol particles, and its essence is still a nano-scale titanium dioxide hydrate. Therefore, after the gel is directly dried, calcined, and crushed, more than 80% of the obtained titanium dioxide is nano-scale. Since the particle size of the titanium dioxide is too small, it is easy to make the column pressure of the chromatographic column too high after filling it into the chromatographic column, thereby increasing the elution loss rate and 68 Ge leakage rate; when glacial acetic acid is used as an inhibitor, although some micron-sized titanium dioxide particles (nano-sized titanium dioxide is formed by aggregation) can be screened out, the yield is generally less than 20%, and the yield is unstable. At the same time, the adsorption performance and leakage rate of the micron-sized titanium dioxide particles do not meet the requirements.

[0086] Based on this, the present application carried out secondary gelation in the titanium source gelation stage, heated and kept the first gel to make it recrystallize, thereby making the nano-scale sol particles aggregate and grow into the first gel. After secondary heating and keeping, the particle size of the sol particles aggregated to form the second gel, thereby making the calcined and crushed titanium dioxide exist in micron-level particle size.

[0087] It should be noted that in order to make titanium dioxide reach a micron-level particle size, the inhibitor for preparing the titanium source solution must be limited to glacial acetic acid; inhibitors in the prior art generally include glacial acetic acid, ethanolamine, ammonia water, acetylacetone, etc., but the applicant found that adding other inhibitors, even after secondary gelation, could not screen out micron-level titanium dioxide that meets the requirements, and only when the inhibitor is glacial acetic acid can the above requirements be met.

[0088] However, the applicant further discovered that under the premise that the inhibitor is glacial acetic acid, the leakage rate and elution efficiency of the micron-sized titanium dioxide screened after the first calcination are not ideal, regardless of whether it is a primary gel or a secondary gel.

[0089] This is because the micron-sized titanium dioxide obtained by the first calcination is obtained by further aggregation of nano-sized titanium dioxide during the second gelation. Under the conditions of the first calcination, the nano-sized titanium dioxide crystals that aggregate to form micron-sized titanium dioxide are too small, resulting in an excessively large specific surface area of ​​the material and too many surface active sites, which leads to a high adsorption capacity of the material for germanium and gallium, making it difficult to achieve the separation effect. On the other hand, the titanium dioxide surface obtained after the first calcination has a large number of extremely fine particles adhered to it, resulting in a rough grain surface and an increase in the specific surface area. In addition, the extremely fine particles are not firmly attached and are washed out with the eluent during elution, resulting in 68 Ge leakage and penetration increased significantly, affecting 68 The elution efficiency of Ga and its stability after multiple elutions.

[0090] In response to the above problems, the applicant found that under the premise of forming micron-sized titanium dioxide, the titanium dioxide particle size is 10-300μm, composed of nano-sized titanium dioxide particles in the range of 10-100nm, and the specific surface area is 30-100m 2 / g, pore size of 5-30nm, smooth surface, anatase phase, it is used as 68 Ge- 68 The performance of the adsorbent of the Ga generator will be greatly improved.

[0091] Based on this, the present invention performs surface modification on the obtained titanium dioxide after the first calcination to make the surface of the titanium dioxide particles smooth and remove the extremely fine particles on the surface; then the titanium dioxide is subjected to a second calcination. The two calcinations make the obtained micron-sized titanium dioxide aggregated to form nano-sized titanium dioxide with a particle size range of 10-100nm, a pore size of 5-30nm, and a specific surface area of ​​30-100m 2 / g, and the surface is smooth and in anatase phase. The titanium dioxide is used for 68 Ge- 68 When Ga generator adsorbent is used, 68 Ge loading activity 68The Ge leakage rate is reduced to about 0.0001%. 68 The Ga elution efficiency is increased to over 75%, and can be maintained above 70% after multiple elutions.

[0092] In the above embodiment, the size range of the nano-titanium dioxide particles formed by controlling the aggregation of micron-sized titanium dioxide is 10-100nm. This is because the nano-particles of titanium dioxide in this size range contain a large number of grain boundaries. These grain boundaries can eliminate crystal defects. Compared with the grains with a size range greater than 100nm, they are more resistant to radiation, thereby improving the performance of micron-sized titanium dioxide. However, the above titanium dioxide has a great influence on the performance of micron-sized titanium dioxide. 68 Ge and 68 Ga has adsorption capacity, so it is necessary to control the pore size of nano-sized titanium dioxide to be in the range of 5-30nm and the specific surface area to be 30-100m 2 / g, increase 68 Gehe 68 The adsorption selectivity of Ga makes the titanium dioxide adsorbent increase 68 The adsorption capacity of Ge is minimized while 68 The adsorption of Ga, therefore 68 Ga elution efficiency is improved and 68 The characteristic of Ge leakage rate reduction.

[0093] The titanium dioxide adsorbent thus prepared has a particle size of 10-300 μm, is composed of 10-100 nm titanium dioxide nanoparticles, and has a specific surface area of ​​30-100 m 2 / g, pore size of 5-30nm, smooth surface, anatase phase standard, so that the titanium dioxide as 68 Ge- 68 When the adsorbent of Ga generator is 68 Ge loading activity 68 The Ge leakage rate is reduced to about 0.0001%. 68 The Ga elution efficiency was increased to over 75%, and could be maintained above 70% during multiple elutions (within a 200-day elution cycle).

[0094] In some optional embodiments, in the titanium source gelation step, the titanium source solution is added dropwise to the purified water solution while stirring, and the stirring speed needs to be controlled to be 10-100 rpm and the drop rate is 1-100 mL / min. This is because the stirring speed and the addition time also have a certain effect on the particle size of the sol particles. Reasonable control of the stirring speed and the addition time is conducive to increasing the particle size of the sol particles forming the first gel, thereby shortening the time for the sol particles to grow from nanoscale to micron scale when forming the second gel, and increasing the amount of micron-sized titanium dioxide after grinding. In this embodiment, the amount of titanium source solution and purified water added can be conventionally selected by those skilled in the art, and the present application preferably has a volume ratio of 1: (0.5-10).

[0095] In some optional embodiments, the heating and holding temperature during the formation of the second gel is 110-180°C, and the holding time is 6-36 hours. The heating and holding temperature and time affect the rate and size of sol particles growing from nanometers to micrometers. Those skilled in the art, after understanding the technical principles of this application, can make conventional selections based on the desired sol particle size. However, in this application, since a larger amount of titanium dioxide of 10-300 microns is desired, the holding temperature is preferably 110-180°C, and the holding time is preferably 6-36 hours.

[0096] In some optional embodiments, the purpose of the surface modification is to obtain a smooth surface and remove extremely fine particles of titanium dioxide on the surface. It can be carried out by oscillation, vortexing, ultrasound, etc. The present application preferably uses ultrasound, and the ultrasound power is 50-1000W and the time is 0.5 to 12h.

[0097] In the examples of the present application, the adsorbent titanium dioxide particles prepared by oscillation, vortexing, ultrasound, etc. have a smooth surface, indicating that there are fewer or no tiny particles adsorbed on the surface and have a certain acid washing resistance. The adsorbent is used for germanium [ 68 Ge]gallium[ 68 Ga] generator, with good elution efficiency, the obtained 68 Ga solution 68 The Ge content is extremely low, which increases the 68 Reliability of Ga solution.

[0098] In some optional embodiments, the solid particles are ground and screened to have a particle size of 30-60 μm, 50-100 μm, 75-150 μm, or 90-180 μm. The applicant has found that the combination of the above particle sizes can further enhance the performance of titanium dioxide as an adsorbent.

[0099] In some optional embodiments, the titanium dioxide particles are smoothed by oscillation, vortexing, ultrasound, etc.

[0100] In some optional embodiments, the first calcination temperature is 300-700°C, and the second calcination temperature is 400-700°C. The applicant has found that the calcination temperature and calcination time affect the specific surface area of ​​titanium dioxide. The above calcination temperature can maximize the surface area of ​​titanium dioxide of 30-100m 2 / g of titanium dioxide with a specific surface area; the calcination time is preferably a first calcination time of 1-12h and a second calcination time of 1-6h.

[0101] It is understood that after the second gel is formed, in order to remove the residual solvent on the surface of the gel, the conventional sol-gel method also includes placing the second gel in an oven for further heating to remove the residual solvent. The drying temperature is preferably 110-180°C, the purpose of which is to remove the organic alcohol and glacial acetic acid remaining on the surface.

[0102] It is understandable that the solid particles need to be placed in a purified water solution during the surface modification to facilitate the removal of extremely fine particles by oscillation and to smooth the surface. In order to enhance its effect, the purified water can also be conventionally replaced with a 0.1 mol / L hydrochloric acid solution. At the same time, after the surface modification, it is necessary to dry the surface until it is dry, and the drying temperature is preferably 110-180°C.

[0103] In the third aspect, the present application embodiment provides a germanium [ 68 Ge]gallium[ 68 Ga] generator, comprising:

[0104] The filler cylinder is filled with the adsorbent described in the first aspect or the adsorbent prepared by the preparation method described in the second aspect, and the adsorbent adsorbs 68 Ge element.

[0105] The adsorbent and preparation method of any of the above embodiments can be used in the embodiments of this application. 68 Ge- 68 The Ga generator will not be described in detail here.

[0106] In some optional embodiments, the adsorbent has a particle size of 10-300 μm, is composed of 10-100 nm nanoparticles, and has a specific surface area of ​​30-100 m 2 / g, pore size of 5-30nm, smooth surface, and granular titanium dioxide in anatase phase.

[0107] The applicant found that the titanium dioxide adsorbent with this performance standard has better adsorption performance and can make 68 Ge- 68 Ga generator 68 The Ge leakage rate is reduced to about 0.0001%, and the activity range is above 30-85mCi level. 68The Ga elution efficiency is increased to over 75%, with a maximum of 86%, and the elution efficiency of multiple elutions can be maintained above 70%.

[0108] It can be understood that the adsorbent particle size described in the present application is 10-300 μm, which means that the titanium dioxide particles with a particle size range of 10-300 μm can be specific particle sizes, such as 10 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, or any range of particle size within 10-300 μm, for example, 10-50 μm, 30-60 μm, 50-150 μm, 20-200 μm, 130-260 μm, 200-300 μm; preferably, the particle size range is 30-60 μm, 50-100 μm, 75-150 μm, 90-180 μm.

[0109] The specific surface area, nanoparticle size, and pore size are as described above. For example, the specific surface area can be 30 m 2 / g, 40m 2 / g、70m 2 / g、85m 2 / g、100m 2 / g, or 30-50m 2 / g, 50-100m 2 / g, 80-100m 2 / g specific surface area range;

[0110] The nanoparticle size can be 10nm, 20nm, 50nm, 60nm, 80nm, 100nm, or in the range of 10-30, 20-60nm, 50-100nm; the pore size can be 5nm, 10nm, 15nm, 20nm, 30nm, or in the range of 5-10nm, 10-25nm, 20-30nm.

[0111] In this embodiment, 10-300 μm granular titanium dioxide can reduce 68 Ge leakage rate, specific surface area affects the crystal structure, thus affecting the yield of titanium dioxide anatase phase, pore size and surface smoothness affect 68 Ga elution efficiency; can only be reduced if titanium dioxide meets the above standards 68 Ge- 68 Ga generator 68 Ge leakage rate and improvement 68 Ga elution efficiency and elution stability.

[0112] In some optional embodiments, germanium [ 68 Ge]gallium[ 68 The Ga] generator includes:

[0113] case;

[0114] Lead shielding body; the lead shielding body is arranged inside the shell, and the lead shielding body is sleeved outside the filling cylinder;

[0115] A rinsing line for rinsing the packing cartridge to obtain gallium [ 68 Ga] element, which runs through the shell and the lead shielding body, and the elution pipeline is connected with the filler cylinder.

[0116] In some optional embodiments, the filler tube is made of a plastic chromatography column, a glass tube, a quartz tube, etc.

[0117] In some optional embodiments, the 68 Ge- 68 The Ga generator also includes an elution pipeline and a lead shielding body.

[0118] In some optional embodiments, according to the loaded 68 Ge activity is different, the 68 Ge- 68 Ga generators are divided into different levels. For example, according to the 68 The activity of Ge is different, and 30mCi, 50mCi and 80mCi can be obtained. 68 Ge- 68 Ga generator.

[0119] It should be noted that the above loading activity is only the preferred loading activity of this application and should not be interpreted as a limitation on the loading activity. The titanium dioxide prepared in this application can be prepared into different loading activities such as microcurie, millicurie and hundred millicurie due to its excellent performance. 68 Ge- 68 Ga generator.

[0120] 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 the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0121] Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0122] Example 1 Preparation of titanium dioxide adsorbent

[0123] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isopropanol and mix thoroughly to obtain a clear and transparent solution. Add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution.

[0124] 2. The titanium source solution was added dropwise to 200 mL of purified water at a stirring speed of 55 rpm and a dropping rate of 5 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 150°C in an air-circulating oven for 24 h to obtain a second gel.

[0125] 3. Place the second gel in a muffle furnace and heat to 400°C at a rate of 5°C / min. Calcinate for 4 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 50-180 μm range.

[0126] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 2 hours at an ultrasonic power of 200w, rinse to remove extremely fine particles, wash several times and then dry in an oven at a drying temperature of 150°C. Place the dried solid particles in a muffle furnace and heat to 500°C at a heating rate of 5°C / min. Calcinate for 3 hours, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0127] Example 2 Preparation of titanium dioxide adsorbent

[0128] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of anhydrous ethanol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0129] 2. The titanium source solution was added dropwise to 1500 mL of purified water at a stirring speed of 10 rpm and a dropping rate of 50 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 110°C in an air-circulating oven for 26 h to obtain a second gel.

[0130] 3. Place the second gel in a muffle furnace and heat to 300°C at a rate of 5°C / min. Calcinate for 1 hour, then allow to cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 10-300 μm range.

[0131] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 6 hours at an ultrasonic power of 50w, rinse to remove extremely fine particles, wash several times and then dry in an oven at 150°C. Place the dried solid particles in a muffle furnace and heat to 400°C at a heating rate of 5°C / min. Calcinate for 1 hour, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0132] Example 3 Preparation of titanium dioxide adsorbent

[0133] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of n-butanol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0134] 2. The titanium source solution was added dropwise to 3000 mL of purified water at a stirring speed of 100 rpm and a dropping rate of 100 mL / min while stirring. The mixture was allowed to stand at room temperature for 24 hours to convert into a first gel. The first gel was then heated to 180°C in an air-circulating oven for 36 hours to obtain a second gel.

[0135] 3. Place the second gel in a muffle furnace and heat to 700°C at a rate of 5°C / min. Calcinate for 12 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 75-150 μm range.

[0136] 4. Place the screened solid particles in a 0.1M HCl solution and ultrasonicate for 12 hours at an ultrasonic power of 1000w. Rinse to remove extremely fine particles. After multiple washings, dry them in an oven at 150°C. Place the dried solid particles in a muffle furnace and heat them to 700°C at a heating rate of 5°C / min. Calcinate for 6 hours, cool them naturally at room temperature, and take them out to obtain a titanium dioxide adsorbent.

[0137] Example 4 Preparation of titanium dioxide adsorbent

[0138] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isoamyl alcohol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0139] 2. The titanium source solution was added dropwise to 800 mL of purified water at a stirring speed of 80 rpm and a dropping rate of 20 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 165°C in an air-circulating oven for 35 h to obtain a second gel.

[0140] 3. Place the second gel in a muffle furnace and heat to 550°C at a rate of 5°C / min. Calcinate for 4.5 hours, then allow to cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 50-100 μm range.

[0141] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 8 hours at an ultrasonic power of 120w, rinse to remove extremely fine particles, wash several times, and then dry in an oven at 150°C. The dried solid particles are placed in a muffle furnace and heated to 550°C at a heating rate of 5°C / min. Calcinate for 2 hours, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0142] Example 5 Preparation of titanium dioxide adsorbent

[0143] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isoamyl alcohol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0144] 2. The titanium source solution was added dropwise to 2200 mL of purified water at a stirring speed of 30 rpm and a dropping rate of 70 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 170°C in an air-circulating oven for 30 h to obtain a second gel.

[0145] 3. Place the second gel in a muffle furnace and heat to 600°C at a rate of 5°C / min. Calcinate for 8 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 90-180 μm range.

[0146] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 1 hour at an ultrasonic power of 800w, rinse to remove extremely fine particles, wash several times and then dry in an oven at 150°C. Place the dried solid particles in a muffle furnace and heat to 650°C at a heating rate of 5°C / min. Calcinate for 5 hours, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0147] Example 6 Preparation of titanium dioxide adsorbent

[0148] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isoamyl alcohol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0149] 2. The titanium source solution was added dropwise to 1000 mL of purified water at a stirring speed of 100 rpm and a dropping rate of 100 mL / min while stirring. The mixture was allowed to stand at room temperature for 24 hours to convert into a first gel. The first gel was placed in an air-circulating oven and heated to 180°C for 30 hours to obtain a second gel.

[0150] 3. Place the second gel in a muffle furnace and heat to 300°C at a rate of 5°C / min. Calcinate for 12 hours, then allow to cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 75-150 μm range.

[0151] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 5 hours at an ultrasonic power of 50w, rinse to remove extremely fine particles, wash several times and then dry in an oven at a drying temperature of 120°C. Place the dried solid particles in a muffle furnace and heat to 500°C at a heating rate of 5°C / min. Calcinate for 5 hours, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0152] Example 7 Preparation of titanium dioxide adsorbent

[0153] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isoamyl alcohol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0154] 2. The titanium source solution was added dropwise to 500 mL of purified water at a stirring speed of 10 rpm and a dropwise addition rate of 5 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 120°C in an air-circulating oven for 30 h to obtain a second gel.

[0155] 3. Place the second gel in a muffle furnace and heat to 500°C at a rate of 5°C / min. Calcinate for 3 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 50-150μm range.

[0156] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 1 hour at an ultrasonic power of 100W, rinse to remove extremely fine particles, wash several times and then dry in an oven at a drying temperature of 130°C. Place the dried solid particles in a muffle furnace and heat to 550°C at a heating rate of 5°C / min. Calcinate for 2 hours, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0157] Example 8 Preparation of titanium dioxide adsorbent

[0158] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of anhydrous ethanol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0159] 2. The titanium source solution was added dropwise to 1200 mL of purified water at a stirring speed of 13 rpm and a dropping rate of 55 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 130°C in an air-circulating oven for 26 h to obtain a second gel.

[0160] 3. Place the second gel in a muffle furnace and heat to 380°C at a rate of 5°C / min. Calcinate for 2 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 50-300 μm range.

[0161] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 6 hours at an ultrasonic power of 50w, rinse to remove extremely fine particles, wash several times and then dry in an oven at a drying temperature of 130°C. Place the dried solid particles in a muffle furnace and heat to 400°C at a heating rate of 5°C / min. Calcinate for 1 hour, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0162] Example 9 Preparation of titanium dioxide adsorbent

[0163] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isoamyl alcohol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0164] 2. The titanium source solution was added dropwise to 2000 mL of purified water at a stirring speed of 38 rpm and a dropping rate of 95 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 170°C in an air-circulating oven for 30 h to obtain a second gel.

[0165] 3. Place the second gel in a muffle furnace and heat to 570°C at a rate of 5°C / min. Calcinate for 8 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 75-180 μm range.

[0166] 4. Place the screened solid particles in a 0.1M HCl solution and ultrasonicate for 2 hours at an ultrasonic power of 800w. Rinse to remove extremely fine particles. After multiple washings, place them in an oven and dry them at a drying temperature of 170°C. Place the dried solid particles in a muffle furnace and heat them to 670°C at a heating rate of 5°C / min. Calcinate for 5 hours, cool them naturally at room temperature, and take them out to obtain a titanium dioxide adsorbent.

[0167] Comparative Example 1 Preparation of titanium dioxide adsorbent

[0168] The preparation was carried out by the existing sol-gel method, wherein the inhibitor was ammonia water (30%), specifically:

[0169] 1. Add 50 mL of tetraisopropyl titanate dropwise to 200 mL of isopropyl alcohol and mix well to obtain a clear solution.

[0170] 2. Add ammonia (30%) dropwise to the above clear solution while stirring to adjust the pH to ≥ 7, and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0171] 3. Add the titanium source solution dropwise into 200 mL of purified water while stirring, and leave it at room temperature for 24 hours to convert it into the first gel. Place the gel on a rotary evaporator at 90°C to remove the solvent.

[0172] 4. Place the first gel in a muffle furnace and heat to 400°C at a rate of 5°C / min. Calcinate for 4 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to obtain a yellow-white solid powder.

[0173] Screening results: Comparative Example 1 uses titanium dioxide prepared by the traditional sol-gel method, and the inhibitor is limited to ammonia water (30%). After grinding, it is impossible to screen out relatively dense titanium dioxide particles in the range of 10-300μm, which is difficult to use as an adsorption filler for a nuclide generator.

[0174] Comparative Example 2 Preparation of titanium dioxide adsorbent

[0175] The preparation is carried out by the existing sol-gel method, wherein glacial acetic acid is selected as the inhibitor, specifically:

[0176] 1. Add 50 mL of tetraisopropyl titanate dropwise to 200 mL of isopropyl alcohol and mix well to obtain a clear solution.

[0177] 2. Add 50 mL of glacial acetic acid dropwise to the above clear and transparent solution while stirring, and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0178] 3. Add the titanium source solution dropwise into 200 mL of purified water while stirring, and leave it at room temperature for 24 hours to convert it into the first gel. Place the gel on a rotary evaporator at 90°C to remove the solvent.

[0179] 4. Place the first gel in a muffle furnace and heat to 400°C at a rate of 5°C / min. Calcinate for 4 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to obtain a black or yellowish-white solid powder.

[0180] Screening results: Comparative Example 2 uses the traditional sol-gel method to prepare titanium dioxide, and the inhibitor is limited to glacial acetic acid. After grinding, the titanium dioxide particles in the range of 10-300 μm are screened out with a yield of 18%. The yield is too low and there are too many impurities, making it difficult to use as 68 Ge- 68 Ga generator adsorbent.

[0181] Comparative Example 3 Preparation of titanium dioxide adsorbent

[0182] The preparation method is the same as that of Example 1, except that, in Comparative Example 3, the titanium dioxide particles obtained by screening after the first calcination (step 3) are directly used without performing step 4.

[0183] Comparative Example 4 Preparation of Titanium Dioxide Adsorbent

[0184] The preparation method is the same as that of Example 1, except that, in Comparative Example 4, the titanium dioxide particles after ultrasonic cleaning and drying in Step 4 are directly used without the subsequent secondary calcination process.

[0185] Comparative Example 5 Preparation of Titanium Dioxide Adsorbent

[0186] The preparation method is the same as that of Example 1, except that, in Comparative Example 5, the titanium dioxide particles obtained by screening after the first calcination (step 3) are directly subjected to a second calcination without performing an ultrasonic cleaning process.

[0187] Comparative Example 6 Preparation of Titanium Dioxide Adsorbent

[0188] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isoamyl alcohol and mix well to obtain a clear and transparent solution; add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution;

[0189] 2. Pour the titanium source solution directly into 300 mL of purified water and leave it at room temperature for 24 hours to convert it into the first gel. Heat the first gel to 180°C in an air circulation oven for 30 hours to obtain the second gel.

[0190] 3. Place the second gel in a muffle furnace and heat to 700°C at a rate of 5°C / min. Calcinate for 12 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 50-150μm range.

[0191] 4. Place the screened solid particles in a 0.1M HCl solution and ultrasonicate for 5 hours at an ultrasonic power of 1000w to remove extremely fine particles. After multiple washings, place them in an oven and dry them at a drying temperature of 160°C to obtain a titanium dioxide adsorbent.

[0192] Comparative Example 7 Preparation of Titanium Dioxide Adsorbent

[0193] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isopropanol and mix thoroughly to obtain a clear and transparent solution. Add 50 mL of glacial acetic acid dropwise to the clear and transparent solution and let it stand at room temperature for 24 hours to obtain a titanium source solution.

[0194] 2. The titanium source solution was added dropwise to 200 mL of purified water at a stirring speed of 55 rpm and a dropping rate of 5 mL / min while stirring. The solution was allowed to stand at room temperature for 24 h to convert into a first gel. The first gel was then heated to 120°C in an air-circulating oven for 24 h to obtain a second gel.

[0195] 3. Place the second gel in a muffle furnace and heat to 700°C at a rate of 5°C / min. Calcinate for 14 hours, then cool naturally to room temperature. Remove the gel and grind it in a mortar. Sieve through a mesh to screen for solid particles in the 50-180 μm range.

[0196] 4. Place the screened solid particles in a 0.1M HCl solution, ultrasonicate for 2 hours at an ultrasonic power of 500w, rinse to remove extremely fine particles, wash several times and then dry in an oven at a drying temperature of 120°C. Place the dried solid particles in a muffle furnace and heat to 700°C at a heating rate of 5°C / min. Calcinate for 6 hours, cool naturally to room temperature, and take out to obtain a titanium dioxide adsorbent.

[0197] Application Example 1 Preparation of 2mCi-level 68 Ge- 68 Ga generator

[0198] First, weigh 5g of the adsorbent prepared in the examples and comparative examples and place it in a glass tube with a sand core, add glass wool and a sieve plate to compact it, and assemble it into a generator cold column. Then use 250mL of 0.1M hydrochloric acid solution to rinse the cold column. Then place the TiO2 cold column in a lead shield, assemble the lead shield, generator housing and accessories to assemble a cold generator. Take 2mCi 68 The Ge solution was placed in a vial and injected by positive pressure injection of the syringe. 68 Inject the Ge solution into the cold generator, continue to pressurize the air, empty the residual liquid in the column, then slowly elute the column with 250mL of 0.1M hydrochloric acid solution, pressurize the air, empty the residual liquid in the column, and obtain 2mCi level 68 Ge- 68 Ga generator.

[0199] Application Example 2 Preparation of 30mCi or above 68 Ge- 68 Ga generator

[0200] First, weigh 5g of the adsorbent prepared in Example 1 and place it in a glass tube with a sand core. Then add glass wool and a sieve plate to compact it and assemble it into a generator cold column. Then rinse the cold column with 250mL of 0.1M hydrochloric acid solution. Then place the TiO2 cold column in a lead shield, assemble the lead shield, generator housing and accessories to form a cold generator. Take 30-85mCi of 68 The Ge solution was placed in a vial and injected by positive pressure injection of the syringe. 68 The Ge solution was injected into the cold generator, and the air was continuously injected to drain the residual liquid in the column. Then 250 mL of 0.1 M hydrochloric acid solution was used to slowly elute the column, and the air was injected to drain the residual liquid in the column. 30 mCi, 50 mCi, and 85 mCi-level Ge were obtained. 68 Ge- 68Ga generator, and long-term elution to investigate relevant performance indicators.

[0201] Test Example 1 2mCi level 68 Ge- 68 Performance investigation of Ga generator

[0202] 68 Ge- 68 Ga generator elution: Take 2mL of 0.1M hydrochloric acid solution into a 10mL sterile syringe, slowly elute the generator by positive pressure injection, and pressurize air to empty the residual liquid in the column, collect the eluent into a sterile vial, and obtain gallium chloride [ 68 Ga] solution. The activity of the eluent was measured and the 2mCi level was obtained. 68 Ge- 68 The elution efficiency of Ga generator, 68 The leakage rate and the elution efficiency of multiple elutions.

[0203] Test Example 2: 30mCi or above 68 Ge- 68 Performance investigation of Ga generator

[0204] 68 Ge- 68 Ga generator elution: Take 5mL of 0.1M hydrochloric acid solution into a 10mL sterile syringe, slowly elute the generator by positive pressure injection, and pressurize air to empty the residual liquid in the column, collect the eluent into a sterile penicillin bottle, and obtain gallium chloride [ 68 Ga] solution. The activity of the eluent was measured and the activity of 30mCi, 50mCi, and 85mCi was obtained. 68 Ge- 68 The elution efficiency of Ga generator, 68 The leakage rate and the elution efficiency of multiple elutions.

[0205] Experimental results:

[0206] Table 1-1. 2mCi level in application example 1 68 Ge- 68 Ga generator performance test;

[0207] Table 1-2. 2mCi level in application example 1 68 Ge- 68 Ga generator performance test;

[0208] Table 2. 30mCi and above in Application Example 1 68 Ge- 68 Elution efficiency of Ga generator;

[0209] Table 3. 30mCi and above in Application Example 1 68 Ge-68 Ga generator 68 Ge leakage rate;

[0210] Table 4. Common commercially available 68 Ge- 68 Ga generator performance.

[0211] Table 1-1

[0212] Result analysis: From Table 1-1, it can be seen that the adsorbent used in Example 1-5 prepared 2mCi 68 Ge- 68 Ga generator, 68 Ge leakage rate is ≤0.0001%, in line with 68 Ge- 68 The basic performance and quality requirements of Ga generators can be used for 68 Ge- 68 Commercial development of Ga generator. It can be seen that compared with the existing technology 68 Ge- 68 The performance of the Ga generator is compared to that of 2mCi 68 Ge- 68 The initial elution efficiency of the Ga generator is consistent with the existing technology. This is because 68 Ge- 68 The elution efficiency of Ga generator is 68 There is a certain relationship between Ge loading activity and the range of 2-30mCi. 68 Ge loading activity is small and in an unsaturated state, so the elution efficiency is not significantly improved or the improvement is not obvious. 68 The Ge leakage rate is significantly reduced, indicating that the performance of the titanium dioxide prepared by the preparation method of the present application is significantly improved compared with the prior art; on the other hand, the preparation method of Comparative Example 1 (replacing the inhibitor with ammonia water) or Comparative Example 2 (not performing secondary gelation) cannot prepare micron-sized titanium dioxide or the yield is too low, while the adsorbents prepared by Comparative Example 3, Comparative Example 4, and Comparative Example 5 are used for 68 Ge- 68 The performance of the Ga generator is too low, its elution efficiency is low, and 68 Ge leakage is much higher than 0.001%, which is difficult to use for commercial development. It is explained that when using the sol-gel method to prepare titanium dioxide, the inhibitor needs to be clearly glacial acetic acid, and it needs to be calcined and cleaned in the state of secondary gel, and the specific calcination temperature and time must be controlled to prepare titanium dioxide nanoparticles with a particle size of 10-300μm, a size range of 10-100nm, a pore size of 5-30nm, and a specific surface area of ​​30-100m 2 / g, and the surface is smooth, in the anatase phase of titanium dioxide, the titanium dioxide as an adsorbent can improve 68 Ge- 68 Performance of Ga generator.

[0213] Furthermore, the titanium dioxide prepared in Comparative Examples 1-5 has no commercial development prospects, while the titanium dioxide adsorbents prepared in Examples 1-5 have similar performances. Therefore, subsequent experiments will compare Example 1 with the prior art.

[0214] Table 1-2

[0215] It can be seen from the above table that the adsorbents of Example 1 and Examples 6-9 are anatase type, and the specific surface area of ​​the adsorbent is 30m 2 / g to 100m 2 / g, the average particle size of nanoparticles is between 10nm and 100nm; the pore size of mesopores is between 5nm and 30nm, and the prepared 2mCi 68 Ge- 68 Ga generator, 68 Ge leakage rate is ≤0.0001%, initial elution efficiency is greater than or equal to 71%, in line with 68 Ge- 68 The basic performance and quality requirements of Ga generators can be used for 68 Ge- 68 Commercial development of Ga generator. Compared with other adsorbents, the specific surface area, average particle size of nanoparticles and pore size of other adsorbents affect the 68 Ge- 68 The elution efficiency and leakage rate of the Ga generator are reduced 68 Ge- 68 The quality of the Ga generator is improved, which shows that the titanium dioxide in the embodiment can be used as an adsorbent. 68 Ge- 68 Performance of Ga generator.

[0216] Table 2

[0217] Table 3

[0218] Table 4

[0219] Results analysis: From Table 2 to Table 4, we can see that in the range of 30-85mCi loading activity, the initial elution efficiency is above 80%, with the highest reaching 86%. After long-term elution (average elution time 6 months), the elution efficiency can still be maintained above 70%. 68 Ge- 68 Compared with Ga generator (Table 4),68 Under the premise of reducing the Ge leakage rate (about 0.0001%), the initial elution efficiency is increased to more than 80%, and the elution efficiency after 200 days of elution can still be maintained at more than 70%. 68 Ge- 68 The performance of Ga generators has been greatly improved.

[0220] Table 4 Data on long-term elution efficiency time Description: The existing technology does not make clear provisions for long-term elution efficiency. Different manufacturers have different regulations for long-term elution. Commonly published long-term elution data is 200 days of elution time or 200 elutions. 68 Ge- 68 The validity period of Ga generator is generally up to 12 months. 68 Ge- 68 Ga generators can even last up to 3 years (based on different performance indicators, such as Russia's 68 Ge- 68 Ga generator with elution efficiency ≥ 45%, 68 Ge leakage ≤ 0.005% is valid for up to 3 years), therefore, this application uses 200 days as the long-term elution efficiency comparison time.

[0221] Commercially available titanium dioxide-based 68 Ge- 68 The patents of Ga generators such as those of Russia's Cyclotron, Germany's EZAG, Belgium's IRE ELiT and Canada's Nordion report a long-term elution efficiency of 55% to 65% for one year or 200 elutions, and it is generally difficult to reach more than 70%.

[0222] 5 mL of 0.1 M HCl solution was used to elute the homemade 85 mCi 68 Ge- 68 Ga generator, 85mCi 68 Ge- 68 The Ga generator was made using the adsorbent of Example 1. The change in elution efficiency during long-term elution is shown in FIG6 . The initial elution efficiency was as high as 86%, which was a very high elution efficiency. The elution efficiency slowly decreased with the increase of elution days and showed a fluctuating trend. It reached a minimum value of about 73% on the 245th day. This may be due to the low temperature, which caused the elution efficiency to decrease. It then gradually increased. After one year, the long-term elution efficiency rose to 81%, which was significantly higher than that of titanium dioxide-based products available on the market and reported in literature patents. 68 Ge- 68 Long-term elution efficiency of Ga generator.

[0223] Furthermore, Figure 1 shows the 50mCi level.68 Ge- 68 The elution efficiency change diagram of the Ga generator for 200 days shows that the elution efficiency decreases slowly with the increase of elution times and shows an up-and-down fluctuation trend. Based on the above trend, the change formula (y=(-2.06×10 -4 )x+0.798), and through calculation, it can be concluded that after 12 months, the elution efficiency can still be maintained at more than 70% (according to the formula, the elution days x=365 are substituted into the formula to calculate y=72%). 68 The Ge leakage rate is stable at about 0.0001%, which is much smaller than that of the European Pharmacopoeia gallium chloride [ 68 Ga] solution standard 68 The leakage rate of Ge is limited to ≤0.001%.

[0224] It should be noted that the present application is not limited to the above-mentioned embodiments. The above-mentioned embodiments are merely examples, and any embodiments having substantially the same structure and effect as the technical concept within the scope of the present application are all included in the technical scope of the present application. In addition, without departing from the scope of the present application, any other embodiments that can be conceived by those skilled in the art and that combine some of the constituent elements in the embodiments are also included in the scope of the present application.

Claims

1. A method for using germanium 68 Ge]gallium[ 68 Ga] generator, wherein The adsorbent is used to adsorb 68 Ge element; the adsorbent comprises: a plurality of titanium dioxide particles, the adsorbent satisfies the following conditions: 1) The specific surface area of ​​the adsorbent is 30m 2 / g to 100m 2 / g; 2) The titanium dioxide particles are composed of a plurality of nanoparticles, and the average particle size of the plurality of nanoparticles is 10 nm to 100 nm; the nanoparticles include mesopores, and the pore size of the mesopores is 5 nm to 30 nm.

2. The adsorbent according to claim 1, wherein The specific surface area of ​​the adsorbent is 31 m 2 / g to 97m 2 / g; the average particle size of the plurality of nanoparticles is 12nm to 96nm; the pore size of the mesopores is 5.7nm to 19nm.

3. The adsorbent according to claim 1 or 2, wherein The crystal phase type of the adsorbent is anatase type.

4. The adsorbent according to any one of claims 1 to 3, wherein The average particle size of the adsorbent is 10 μm to 300 μm.

5. The adsorbent according to any one of claims 1 to 4, wherein The pore volume of the adsorbent is 0.1 cm 3 / g to 0.5cm 3 / g.

6. The adsorbent according to any one of claims 1 to 5, wherein The adsorbent includes: one or more of the titanium dioxide particles with an average particle size of 30-60 μm, the titanium dioxide particles with an average particle size of 50-100 μm, the titanium dioxide particles with an average particle size of 75-150 μm, and the titanium dioxide particles with an average particle size of 90-180 μm.

7. The adsorbent according to any one of claims 1 to 6, wherein The titanium dioxide particles are treated by any one or more methods of oscillation, vortexing, and ultrasound to make the surface of the titanium dioxide particles smooth.

8. A method for 68 Ge- 68 A method for preparing a titanium dioxide adsorbent for a Ga generator, wherein: The sol-gel method is used to prepare the product, which comprises the following steps: Dissolving the titanium source in organic alcohol and then adding glacial acetic acid to obtain a titanium source solution; Adding the titanium source solution dropwise into the purified aqueous solution while stirring, and letting it stand to obtain a first gel, and heating and retaining the first gel to obtain a second gel; After the second gel is formed by the first calcination, solid particles with a particle size of 10-300 μm are ground and screened for surface modification, and then subjected to the second calcination to obtain an adsorbent.

9. The preparation method according to claim 8, wherein: The preparation method satisfies one or more of the following conditions: 1) The stirring speed of the dropwise addition while stirring is 10-100 rpm, and the dropwise addition rate is 1-100 mL / min; 2) The volume ratio of the titanium source solution to purified water is 1:(0.5-10); 3) The heating and heat preservation temperature is 110-180° C. and the time is 6-36 hours; 4) using ultrasonic treatment to modify the surface of the solid particles, the ultrasonic power is 50-1000W, and the time is 0.5-12h; 5) Grinding and screening solid particles with particle sizes of 30-60μm, 50-100μm, 75-150μm, and 90-180μm; 6) the first calcination temperature is 300-700° C., and the second calcination temperature is 400-700° C.; 7) The first roasting time is 1-12 hours, and the second roasting time is 1-6 hours.

10. A Germanium 68 Ge]gallium[ 68 Ga] generator, comprising: A filling cylinder, wherein the filling cylinder is filled with the adsorbent according to any one of claims 1 to 7 or the adsorbent prepared by the preparation method according to claim 8 or 9, and the adsorbent adsorbs 68 Ge element.

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