An adsorbent for a germanium 68 gallium 68 gallium generator and a method of preparation

Abstract

The application relates to a kind of 68 Ge- 68 The preparation method of Ga generator adsorbent belongs to the field of radioactive material application. In view of the problems that the existing technology is used for 68 Ge- 68 The leaching efficiency of the titanium dioxide adsorbent of Ga generator 68 There is room for improvement, and the leaching efficiency is significantly reduced after multiple leaching. A preparation method of titanium dioxide is provided. The titanium dioxide particles prepared by the method have a particle size of 10-300 μm, are composed of 10-100 nm nanoparticles, have a specific surface area of 30-100 m 2 / g, a pore size of 5-30 nm, and a smooth surface, and are in an anatase phase. As 68 Ge- 68 The adsorbent of Ga generator, in the activity range of 30 mCi or more, 68 The Ge leakage rate is reduced to about 0.0001%, the initial 68 The Ga leaching efficiency is increased to more than 75%, and multiple leaching can be maintained at more than 70%.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of germanium[ 68 Ge] gallium[ 68 Ga] generator adsorbent preparation method, belongs to the field of radioactive materials application. BACKGROUND

[0002] Radionuclide gallium-68 ( 68 Ga) is emitted by β + Decay of positron, half-life (T 1 / 2 ) is 67.71 min, maximum energy is 1.899 MeV, average energy 0.836 MeV, decay daughter is zinc-68 ( 68 Zn). Wherein positron annihilation radiation occurs, emits 0.511 MeV characteristic gamma rays, is used for positron emission computed tomography (Positron Emission Tomography, PET), and more and more is applied in various diseases such as cancer, infection, nervous system and cardiovascular system and so on PET imaging diagnosis, is a kind of medical radionuclide with integrated diagnosis and individualized medical prospects.

[0003] Germanium[ 68 Ge] gallium[ 68 Ga] generator ( 68 Ge- 68 Ga generator) is 68 Ga radionuclide very important source, its separation mechanism is based on solid adsorbent only adsorbing parent nuclide 68 Ge, and for daughter nuclide 68 Ga almost no adsorption principle, with hydrochloric acid solution regular elution chromatographic column can 68 Ga is separated from 68 Ge, therefore, adsorption filler is the key core technology, its performance is very important for the leakage rate of 68 Ge and 68 Ga elution efficiency.

[0004] As early as the 1970s and 1980s, TiO2 was used as an adsorbent for 68 Ge and 68 Ga adsorption research (Radiokhimiya, 1975, 17, 137−140). Until 1996, the Russian cyclotron company first supplied 68 Ge- 68 Ga generator based on modified TiO2 material to the market, and its elution efficiency for 68 Ga is 60%-75%, and for 68The Ge leakage rate is approximately 0.001% (Journal of Nuclear Medicine and Molecular Imaging, 2019, 9, 30−66). In recent years, companies such as Eckert & Ziegler in Germany and IRE EliT in Belgium have also developed commercially viable materials based on TiO2. 68 Ge- 68 Ga generator. US Patent US10357758B2 also discloses a method for preparing chromatographic adsorption materials for radionuclide generators, which can prepare adsorption materials of metal oxides such as titanium dioxide and tin dioxide. The preparation process involves dissolving TiCl4 in concentrated hydrochloric acid, then neutralizing it with an alkaline solution such as ammonia. The resulting solid is then calcined and ultrasonically cleaned to obtain the chromatographic adsorption material. This material was used to prepare 30 mCi-level... 68 Ge- 68 Ga generator, for 68 The initial rinsing efficiency of Ga is around 75%, and the rinsing efficiency after multiple rinsings can be stabilized at over 65%. 68 Ge leakage rate meets European Pharmacopoeia standards for gallium chloride. 68 Ga] solution standard (≤0.001%).

[0005] It can be seen that existing technologies utilize titanium dioxide as an adsorbent while ensuring... 68 Ge's leakage rate meets the European Pharmacopoeia requirements for gallium chloride. 68 Under the premise that the Ga] solution standard is ≤0.001%, 68 The rinsing efficiency of Ga is generally around 60%-75%, and it decreases further after multiple rinsings, potentially even falling below 55%. However, existing technologies can improve this. 68 The rinsing efficiency of Ga is often accompanied by 68 Ge's leakage rate is also relatively higher, and those skilled in the art should know that a higher... 68 Ga rinsing efficiency and lower 68 Ge leakage rate indicates superior adsorbent performance.

[0006] On the other hand, used for 68 Ge- 68 The TiO2 used in Ga generators requires micron-sized particles, but existing technologies mostly employ sulfuric acid and chlorination methods, which require strong acids (sulfuric acid, hydrochloric acid, etc.) and chlorine gas. The resulting materials are mostly powders, and these processes are complex, energy-intensive, generate a lot of waste, have high metal impurity content, and complex crystal structures, making them unsuitable for use in Ga production. 68 Ge- 68 The adsorption packing material for the Ga generator.

[0007] Based on the above analysis, there is still a need in this field for an environmentally friendly, simple, efficient, and convenient preparation method that also has lower costs. 68 Ge leakage rate and higher stability 68 TiO2 adsorbent with high Ga leaching efficiency. Summary of the Invention

[0008] In view of the above problems, the purpose of the present invention is to provide a method for 68 Ge- 68 The preparation method of the Ga generator adsorbent and the obtained adsorbent are described. This adsorbent exhibits excellent and stable properties and serves as... 68 Ge- 68 The adsorbent in the Ga generator has an activity range of 30 mCi or higher. 68 The Ge leakage rate decreased to approximately 0.0001%, initially. 68 The Ga rinsing efficiency is increased to over 75%, and it can be maintained above 70% even after multiple rinsings.

[0009] To achieve the above objectives, the technical solution of the present invention provides a method for... 68 Ge- 68 A method for preparing titanium dioxide adsorbent for a Ga generator, wherein the adsorbent is prepared by a sol-gel method, comprising the following steps:

[0010] The titanium source was dissolved in an organic alcohol and then glacial acetic acid was added to obtain a titanium source solution.

[0011] The titanium source solution was added dropwise to the purified aqueous solution while stirring, and the mixture was allowed to stand to obtain the first gel. The first gel was then heated and kept warm, and then recrystallized to obtain the second gel.

[0012] After the second gel is calcined and shaped, it is crushed, screened, and surface-modified with solid particles of 10-300 μm in size, and then calcined again to obtain the adsorbent.

[0013] Preferably, the stirring speed of the method of adding dropwise while stirring is 10-100 rpm and the dropping speed is 1-100 mL / min.

[0014] Preferably, the volume ratio of the titanium source solution to purified water is 1:(0.5-10).

[0015] Preferably, the heating and heat preservation temperature is 110-180℃, and the time is 6-36h.

[0016] Preferably, the solid particles are surface modified by ultrasonic treatment, wherein the ultrasonic power is 50-1000W and the time is 0.5-12h.

[0017] Preferably, the solid particles are ground and screened to have a particle size of 30-60μm, 50-100μm, 75-150μm, or 90-180μm.

[0018] Furthermore, the first calcination temperature is 300-700℃, and the second calcination temperature is 400-700℃.

[0019] Furthermore, the first roasting time is 1-12 hours, and the second roasting time is 1-6 hours.

[0020] And the titanium dioxide adsorbent prepared according to the above preparation method.

[0021] The present invention has the following beneficial effects:

[0022] 1. This invention employs an improved sol-gel method to prepare titanium dioxide adsorbents. On the one hand, the process is simple, environmentally friendly, and poses no risk of introducing other metal ions. It is highly efficient and convenient to prepare, and can be mass-produced. On the other hand, it overcomes the problem that titanium dioxide prepared by the existing sol-gel method is nanoscale and cannot be used as an adsorbent for germanium-gallium generators. The titanium dioxide prepared by the sol-gel method is micrometer-scale and exhibits excellent performance when used as an adsorbent for germanium-gallium generators.

[0023] 2. The titanium dioxide adsorbent prepared by this invention has a particle size of 10-300 μm, is composed of 10-100 nm nanoparticles, and has a specific surface area of ​​30-100 m². 2 / g, with a pore size of 5-30nm and a smooth surface, exhibiting anatase phase. It is used as an adsorbent for... 68 Ge- 68 Ga generator, significantly improved 68 Ge- 68 The performance of Ga generators, especially for activity ranges above 30 mCi. 68 The Ge leakage rate decreased to approximately 0.0001%, initially 68 The Ga rinsing efficiency is increased to over 75%, and it can be maintained above 70% even after multiple rinsings. Attached Figure Description

[0024] Appendix Figure 1 X-ray diffraction pattern of modified TiO2 particulate material;

[0025] Appendix Figure 2 Scanning electron microscope (SEM) images of modified TiO2 particulate materials;

[0026] Appendix Figure 3 Scanning electron microscope (SEM) images of modified TiO2 particulate materials;

[0027] AppendixFigure 4 Scanning electron microscope (SEM) images of modified TiO2 particulate materials;

[0028] Appendix Figure 5 50mCi 68 Ge- 68 Changes in rinsing efficiency of Ga generator over 200 days and linear fitting graph. Detailed Implementation

[0029] The embodiments of the present invention will be described in detail below with reference to examples. Those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions in the examples are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products. Unless otherwise specified, all quantities listed are based on total weight and described in parts by weight. The present invention should not be construed as being limited to the specific embodiments described.

[0030] Unless otherwise specified, the technical terms in this specification have the same meaning as those generally understood by those skilled in the art; however, in case of any conflict, the definitions in this specification shall prevail.

[0031] The term "rinsing efficiency" refers to the efficiency of rinsing when the parent nuclide... 68 Ge decays into daughter nuclides 68 After Ga, the collected samples were rinsed with an eluent. 68 The ratio of the actual quantity of Ga to the theoretical quantity.

[0032] The term "bleed-through rate" refers to the percentage of holes that can be bleed through a rinsing agent. 68 Ge leaching rate.

[0033] The term "specific surface area" refers to the total area of ​​a unit mass of adsorbent material, which can be measured by the gas adsorption method.

[0034] The term "pore size" refers to the size of the pores inside micron-sized titanium dioxide (micron-sized titanium dioxide is formed by the aggregation of nano-sized titanium dioxide particles, and the pore size is the size of the pores between and inside the nano-sized titanium dioxide particles).

[0035] The term "titanium dioxide particle size" refers to the size of titanium dioxide micron-sized particles, which are composed of aggregates of nanoparticles.

[0036] The term "nanoparticles" refers to nano-sized titanium dioxide particles that aggregate to form micron-sized titanium dioxide particles.

[0037] In the context of this invention, the terms "comprising" or "including" do not exclude other possible elements. The compositions of this invention (including the various embodiments described herein) may comprise, consist of, or consist substantially of the following elements; the essential elements and necessary limitations of the invention as described herein; and any other or optional ingredients, components, or limitations as described herein or as otherwise desired.

[0038] The invention will now be described in more detail. It should be noted that the various aspects, features, implementation methods, examples, and advantages of the invention described herein are compatible and / or can be combined together.

[0039] The embodiments of this application disclose a method for... 68 Ge- 68 A method for preparing titanium dioxide adsorbent for Ga generators, wherein the adsorbent is prepared by a sol-gel method, comprising the following steps: dissolving a titanium source in an organic alcohol and adding glacial acetic acid to obtain a titanium source solution; adding the titanium source solution dropwise to a purified aqueous solution while stirring, allowing it to stand to obtain a first gel; heating and holding the first gel and recrystallizing it to obtain a second gel; calcining the second gel to form a first gel, grinding and screening solid particles with a particle size of 10-300 μm for surface modification, and then calcining it a second time to obtain the adsorbent.

[0040] In this embodiment, the titanium source solution is prepared by the sol-gel method, that is, the titanium source (e.g., tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate, etc.) is dissolved in an organic alcohol solution, and then an inhibitor (e.g., glacial acetic acid, etc.) is added to inhibit its hydrolysis to form a titanium source solution; this application does not make any particular limitation, but only provides preferred embodiments.

[0041] In a preferred embodiment, the titanium source solution is prepared by:

[0042] S1. Dissolve a titanium source (e.g., tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate, tetrahexyl titanate, etc.) in a C2-C5 alcohol solution, mix thoroughly, and obtain a clear and transparent solution. The purpose of this step is to dissolve the titanium source. Preferably, the volume ratio of the titanium source to the C2-C5 alcohol solution is 2:(0.5-20), more preferably, the titanium source is tetraisopropyl titanate or tetrabutyl titanate, and the alcohol solution is more preferably isopropanol. When the alcohol solution is isopropanol, the volume ratio of the titanium source to isopropanol is more preferably 1:(3-6).

[0043] S2. While stirring, add the obtained clear and transparent solution dropwise to glacial acetic acid to obtain a white turbid solution. After standing for a period of time, a clear and transparent solution is obtained, which is the titanium source solution. The purpose of this step is to inhibit the hydrolysis of the titanium source. The volume ratio of titanium source to glacial acetic acid is preferably 1:(0.5-10), more preferably 1:1.

[0044] Existing technologies generally use methods such as the sulfuric acid process and chlorination process to prepare titanium dioxide. These processes are complex, energy-intensive, generate a lot of waste, and the resulting titanium dioxide has a high content of metallic impurities and a complex crystal form, making it unsuitable for use as a raw material. 68 Ge- 68 Ga generator adsorption packing; US10357758B2 discloses a method for... 68 Ge- 68 The initial adsorption efficiency of titanium dioxide in the Ga generator adsorption packing is 75%, and the long-term rinsing efficiency remains stable at around 65%. Furthermore, according to publicly available data, while meeting the requirements... 68 Ge's leakage rate meets the European Pharmacopoeia requirements for gallium chloride. 68 Under the premise of Ga] solution standard (≤0.001%), 68 The initial elution efficiency of Ga is generally no higher than 75%, and a significant decrease in elution efficiency occurs after multiple elutions. The sol-gel method is simple, rapid, environmentally friendly, and poses no risk of introducing other metal ions, thus gradually becoming a focus of attention for technicians. However, the titanium dioxide prepared by the existing sol-gel method is generally nanoscale. This is because after the titanium source is reacted with organic alcohols and inhibitors to form a titanium source solution, it aggregates in purified water to form sol particles of about 1 nm. Although these sol particles further grow to form a gel during static standing, this gel is merely an overlap between sol particles; its essence remains nanoscale titanium dioxide hydrate. Therefore, after directly drying, calcining, and pulverizing this gel, more than 80% of the obtained titanium dioxide is nanoscale. Due to its small particle size, when this titanium dioxide is packed into a chromatographic column, it easily causes excessive column pressure, increasing the elution loss rate. 68 Ge leakage rate; Although some micron-sized titanium dioxide particles (nano-sized titanium dioxide is formed by aggregation) can be obtained by using glacial acetic acid as an inhibitor, 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.

[0045] Based on this, this application performs secondary gelation in the titanium source gelation stage. The first gel is heated and kept warm to recrystallize it, thereby causing the nano-sized sol particles to aggregate and grow into the first gel. After secondary heating and warming, the particle size of the sol particles aggregates to form the second gel, thus allowing the calcined and crushed titanium dioxide to exist in micron-sized particles.

[0046] It should be noted that in order to achieve a micron-sized titanium dioxide particle size, the inhibitor used to prepare the titanium source solution must be limited to glacial acetic acid. In the prior art, inhibitors generally include glacial acetic acid, ethanolamine, ammonia, acetylacetone, etc. However, the applicant found that even after secondary gelation, it was impossible to obtain micron-sized titanium dioxide that met the requirements when other inhibitors were added. Only when the inhibitor was glacial acetic acid could the above requirements be met.

[0047] However, the applicant further discovered that, with glacial acetic acid as the inhibitor, the permeation rate and rinsing efficiency of the micron-sized titanium dioxide screened after one calcination were not ideal, regardless of whether it was a primary or secondary gel.

[0048] This is because the micron-sized titanium dioxide obtained from a single calcination is obtained through the further aggregation of nano-sized titanium dioxide during a secondary gelation process. Under the conditions of a single calcination, the nano-titanium dioxide grains that aggregate to form micron-sized titanium dioxide are too small, resulting in an excessively large specific surface area and too many surface active sites. This leads to a high adsorption capacity for both germanium and gallium, making it difficult to achieve a separation effect. On the other hand, the surface of the titanium dioxide obtained after a single calcination is adhered to by a large number of extremely fine particles, causing the grain surface to be rough and the specific surface area to increase. Furthermore, the adhesion of these extremely fine particles is not firm, and they are washed out with the rinsing agent during rinsing, leading to... 68 Ge leakage has increased significantly, affecting 68 The rinsing efficiency of Ga and its stability after multiple rinsings.

[0049] To address the aforementioned issues, the applicant discovered that, under the premise of forming micron-sized titanium dioxide, the titanium dioxide particle size is 10-300 micrometers, the titanium dioxide nanoparticle size ranges from 10-100 nm, the pore size is 5-30 nm, and the specific surface area is 30-100 m². 2 When the content is / g and the surface is smooth, exhibiting anatase phase, it is considered as 68 Ge- 68 The performance of the adsorbent in the Ga generator will be greatly improved.

[0050] Based on this, this application 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 it undergoes a second calcination. The two calcinations result in micron-sized titanium dioxide formed by the aggregation of 10-100nm titanium dioxide nanoparticles with a specific surface area of ​​30-100m². 2 / g, with a pore size of 5-30nm and a smooth surface, exhibiting anatase phase, this titanium dioxide is used for 68 Ge- 68 When using Ga generator adsorbents, in different 68 Ge loading activity 68 The Ge leakage rate decreased to approximately 0.0001%, initially 68The Ga rinsing efficiency is increased to over 75%, and it can be maintained above 70% even after multiple rinsing cycles (within a 200-day rinsing cycle).

[0051] In the above embodiments, the size range of the nano-titanium dioxide particles that aggregate to form micron-sized titanium dioxide is controlled to be 10-100 nm. This is because titanium dioxide nanoparticles in this size range contain a large number of grain boundaries. These grain boundaries can eliminate crystal defects, and compared to grains with a size range greater than 100 nm, they are more radiation resistant, thus improving the performance of micron-sized titanium dioxide. However, the above-mentioned titanium dioxide... 68 Gehe 68 Ga has adsorption capacity, therefore it is necessary to control the pore size range of nano-sized titanium dioxide to be 5-30 nm and the specific surface area to be 30-100 m². 2 / g, increasing the effect 68 Gehe 68 The adsorption selectivity of Ga allows this titanium dioxide adsorbent to increase the adsorption of Ga. 68 While maximizing the adsorption capacity of Ge, we should also minimize its impact on... 68 Ga adsorption, therefore exhibiting 68 Ga rinsing efficiency improved 68 The characteristic of reduced Ge leakage rate.

[0052] Therefore, the prepared titanium dioxide adsorbent 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 m². 2 / g, with a pore size of 5-30nm and a smooth surface, exhibiting the standard of anatase phase, making this titanium dioxide a standard for... 68 Ge- 68 When using the adsorbent in a Ga generator, in different... 68 Ge loading activity 68 The Ge leakage rate decreased to approximately 0.0001%, initially 68 The Ga rinsing efficiency is increased to over 75%, and it can be maintained above 70% even after multiple rinsing cycles (within a 200-day rinsing cycle).

[0053] In a further embodiment, during the titanium source gelation step, the titanium source solution is added dropwise to the purified aqueous solution while stirring. The stirring speed needs to be controlled at 10-100 rpm, and the dropping rate at 1-100 mL / min. This is because the stirring speed and dropping time also have a certain impact on the particle size of the sol particles. Reasonably controlling the stirring speed and dropping time is beneficial to increasing the particle size of the sol particles forming the first gel, thereby shortening the time for the sol particles to grow from the nanoscale to the microscale when forming the second gel, and increasing the number of micron-sized titanium dioxide particles after grinding. In this embodiment, the amount of titanium source solution to purified water added can be conventionally selected by those skilled in the art; in this application, a volume ratio of 1:(0.5-10) is preferred.

[0054] In a further embodiment, the heating and holding temperature during the formation of the second gel is 110-180°C, and the time is 6-36 hours. The heating and holding temperature and time affect the rate and size of the sol particles growing from the nanoscale to the microscale. Those skilled in the art, after understanding the technical principles of this application, can conventionally select the appropriate sol particle size based on the desired size. However, in this application, since it is necessary to obtain more 10-300 micrometer-sized titanium dioxide, the holding temperature is preferably 110-180°C, and the holding time is preferably 6-36 hours.

[0055] In a further embodiment, the purpose of the surface modification is to obtain titanium dioxide with a smooth surface and remove extremely fine particles from the surface. This can be done by means of oscillation, vortexing, ultrasound, etc. In this application, ultrasound is preferred, with an ultrasound power of 50-1000W and a duration of 0.5-12h.

[0056] In a preferred embodiment, the crushed and screened solid particles have particle sizes of 30-60μm, 50-100μm, 75-150μm, and 90-180μm; the applicant has found that the combination of the above particle sizes can further improve the performance of titanium dioxide as an adsorbent.

[0057] In a further embodiment, the first calcination temperature is 300-700℃, and the second calcination temperature is 400-700℃. The applicant has found that the calcination temperature and calcination time affect the specific surface area of ​​the titanium dioxide. For example, the higher the calcination temperature and the longer the calcination time, the smaller the specific surface area. Based on this, the aforementioned calcination temperature can maximize the specific surface area to 30-100 μm. 2 / g of titanium dioxide specific surface area; the preferred calcination time is 1-12h for the first calcination time and 1-6h for the second calcination time.

[0058] It is understood that after the second gel is formed, in order to remove the residual solvent on the gel surface, the method disclosed in the conventional sol-gel method is also included, which involves placing the second gel in an oven for further heating to remove the residual solvent. The drying temperature is preferably 110-180°C, and the purpose is to remove the residual organic alcohols and glacial acetic acid on the surface.

[0059] It is understood that during the surface modification, the solid particles need to be placed in a purified aqueous solution to facilitate the removal of extremely fine particles by shaking and to make the surface smooth. In order to enhance its effect, the purified water can also be conventionally replaced with a 0.1 mol / L hydrochloric acid solution. After surface modification, the surface also needs to be dried until it is dry. The drying temperature is preferably 110-180℃. Example

[0060] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and are not intended to limit the scope of the invention.

[0061] Unless otherwise specified, the reagents, methods and equipment used in this invention are conventional in the art.

[0062] Example 1: Preparation of Titanium Dioxide Adsorbent

[0063] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of isopropanol 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 h to obtain a titanium source solution.

[0064] 2. The titanium source solution was added dropwise to 200 mL of purified water while stirring at a stirring speed of 55 rpm and a dropping speed of 5 mL / min. The mixture was left at room temperature for 24 h to form the first gel. The first gel was then placed in an air-circulating oven and heated to 150 °C for 24 h to obtain the second gel.

[0065] 3. Place the second gel in a muffle furnace and heat it to 400℃ at a rate of 5℃ / min, calcine for 4 hours, then allow it to cool naturally to room temperature. Remove it, grind it in a mortar, and sieve it through a mesh to obtain solid particles in the range of 50-180μm.

[0066] 4. Place the screened solid particles in a 0.1M HCl solution and sonicate for 2 hours at a power of 200W. Rinse to remove extremely fine particles. After multiple washes, place the particles in an oven to dry at 150℃. Place the dried solid particles in a muffle furnace and heat to 500℃ at a rate of 5℃ / min. Calcine for 3 hours, allow to cool naturally at room temperature, and remove to obtain the titanium dioxide adsorbent.

[0067] Example 2: Preparation of Titanium Dioxide Adsorbent

[0068] 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 h to obtain a titanium source solution.

[0069] 2. The titanium source solution was added dropwise to 1500 mL of purified water while stirring at a stirring speed of 10 rpm and a dropping speed of 50 mL / min. The mixture was left at room temperature for 24 h to form the first gel. The first gel was then placed in an air-circulating oven and heated to 110 °C for 26 h to obtain the second gel.

[0070] 3. Place the second gel in a muffle furnace and heat it to 300℃ at a rate of 5℃ / min, calcine for 1 hour, then allow it to cool naturally to room temperature. Remove it, grind it in a mortar, and sieve it through a mesh to select solid particles in the range of 10-300μm.

[0071] 4. Place the screened solid particles in a 0.1M HCl solution and sonicate for 6 hours at a power of 50W. Rinse to remove extremely fine particles, and after multiple washes, place them in an oven to dry at 150℃. Place the dried solid particles in a muffle furnace and heat to 400℃ at a rate of 5℃ / min. Calcine for 1 hour, allow to cool naturally at room temperature, and remove to obtain the titanium dioxide adsorbent.

[0072] Example 3: Preparation of Titanium Dioxide Adsorbent

[0073] 1. Add 50 mL of tetrabutyl titanate dropwise to 200 mL of n-butanol 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 h to obtain a titanium source solution;

[0074] 2. The titanium source solution was added dropwise to 3000 mL of purified water while stirring at a stirring speed of 100 rpm and a dropping speed of 100 mL / min. The mixture was left at room temperature for 24 h to form the first gel. The first gel was placed in an air-circulating oven and heated to 180 °C for 36 h to obtain the second gel.

[0075] 3. Place the second gel in a muffle furnace and heat it to 700℃ at a rate of 5℃ / min, calcining for 12 hours, then allow it to cool naturally to room temperature. Remove it, grind it in a mortar, and sieve it through a mesh to select solid particles in the range of 75-150μm.

[0076] 4. Place the screened solid particles in a 0.1M HCl solution and sonicate for 12 hours at a power of 1000W. Rinse to remove extremely fine particles, and after multiple washes, place in an oven to dry at 150℃. Place the dried solid particles in a muffle furnace and heat to 700℃ at a rate of 5℃ / min. Calcine for 6 hours, allow to cool naturally to room temperature, and remove to obtain the titanium dioxide adsorbent.

[0077] Example 4: Preparation of Titanium Dioxide Adsorbent

[0078] 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 h to obtain a titanium source solution;

[0079] 2. The titanium source solution was added dropwise to 800 mL of purified water while stirring at a stirring speed of 80 rpm and a dropping speed of 20 mL / min. The mixture was left at room temperature for 24 h to form the first gel. The first gel was then placed in an air-circulating oven and heated to 165 °C for 35 h to obtain the second gel.

[0080] 3. Place the second gel in a muffle furnace and heat it to 550℃ at a rate of 5℃ / min, calcining for 4.5 hours, then allow it to cool naturally to room temperature. Remove it, grind it in a mortar, and sieve it through a mesh to select solid particles in the range of 50-100μm.

[0081] 4. Place the screened solid particles in a 0.1M HCl solution and sonicate for 8 hours at a power of 120W. Rinse to remove extremely fine particles, and after multiple washes, place in an oven to dry at 150℃. Place the dried solid particles in a muffle furnace and heat to 550℃ at a rate of 5℃ / min. Calcine for 2 hours, allow to cool naturally to room temperature, and remove to obtain titanium dioxide adsorbent.

[0082] Example 5: Preparation of Titanium Dioxide Adsorbent

[0083] 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 h to obtain a titanium source solution;

[0084] 2. The titanium source solution was added dropwise to 2200 mL of purified water while stirring at a stirring speed of 30 rpm and a dropping speed of 70 mL / min. The mixture was left at room temperature for 24 h to form the first gel. The first gel was then placed in an air-circulating oven and heated to 170 °C for 30 h to obtain the second gel.

[0085] 3. Place the second gel in a muffle furnace and heat it to 600℃ at a rate of 5℃ / min, calcine for 8 hours, then allow it to cool naturally to room temperature. Remove it, grind it in a mortar, and sieve it through a mesh to select solid particles in the range of 90-180μm.

[0086] 4. Place the screened solid particles in a 0.1M HCl solution and sonicate for 1 hour at a power of 800W. Rinse to remove extremely fine particles. After multiple washes, place the particles in an oven to dry at 150℃. Place the dried solid particles in a muffle furnace and heat to 650℃ at a rate of 5℃ / min. Calcine for 5 hours, allow to cool naturally at room temperature, and remove to obtain the titanium dioxide adsorbent.

[0087] Comparative Example 1: Preparation of Titanium Dioxide Adsorbent

[0088] The preparation was carried out using the existing sol-gel method, with ammonia (30%) as the inhibitor. Specifically:

[0089] 1. Add 50 mL of tetraisopropyl titanate to 200 mL of isopropanol and mix well to obtain a clear and transparent solution;

[0090] 2. While stirring, add ammonia (30%) dropwise to the above clear and transparent solution to adjust the pH to ≥7, and let it stand at room temperature for 24 hours to obtain the titanium source solution;

[0091] 3. Add the titanium source solution dropwise to 200 mL of purified water while stirring, and let it stand at room temperature for 24 h to form the first gel. Place the gel on a rotary evaporator at 90 °C to remove the solvent.

[0092] 4. Place the first gel in a muffle furnace and heat it to 400℃ at a rate of 5℃ / min. Calcine for 4 hours, then allow it to cool naturally to room temperature. Remove the gel, grind it in a mortar, and sieve it to obtain a yellowish-white solid powder.

[0093] Screening results: Comparative Example 1 used titanium dioxide prepared by the traditional sol-gel method, and the inhibitor was limited to ammonia (30%). After grinding, it was impossible to screen out relatively dense titanium dioxide particles in the range of 10-300μm, which is difficult to use as adsorption packing material for radionuclide generators.

[0094] Comparative Example 2: Preparation of Titanium Dioxide Adsorbent

[0095] The preparation was carried out using the existing sol-gel method, with glacial acetic acid selected as the inhibitor, specifically:

[0096] 1. Add 50 mL of tetraisopropyl titanate to 200 mL of isopropanol and mix well to obtain a clear and transparent solution;

[0097] 2. While stirring, add 50 mL of glacial acetic acid dropwise to the above clear and transparent solution, and let it stand at room temperature for 24 hours to obtain the titanium source solution;

[0098] 3. Add the titanium source solution dropwise to 200 mL of purified water while stirring, and let it stand at room temperature for 24 h to form the first gel. Place the gel on a rotary evaporator at 90 °C to remove the solvent.

[0099] 4. Place the first gel in a muffle furnace and heat it to 400°C at a rate of 5°C / min. Calcine for 4 hours, then allow it to cool naturally to room temperature. Remove the gel, grind it in a mortar, and sieve it to obtain a black or yellowish-white solid powder.

[0100] Screening results: Comparative Example 2, using the traditional sol-gel method to prepare titanium dioxide with glacial acetic acid as the inhibitor, showed titanium dioxide particles ranging from 10 to 300 μm after grinding and screening, with a yield of 18%. This yield was too low and contained too many impurities, making it unsuitable for use as a raw material. 68 Ge- 68 Ga generator adsorbent.

[0101] Comparative Example 3: Preparation of Titanium Dioxide Adsorbent

[0102] The preparation method is the same as in Example 1, except that in Comparative Example 3, the titanium dioxide particles obtained after the first calcination and screening (step 3) are used directly without step 4.

[0103] Comparative Example 4: Preparation of Titanium Dioxide Adsorbent

[0104] The preparation method is the same as in Example 1, except that in Comparative Example 4, the titanium dioxide particles after ultrasonic cleaning and drying in step 4 are used directly without subsequent secondary calcination.

[0105] Comparative Example 5: Preparation of Titanium Dioxide Adsorbent

[0106] The preparation method is the same as in Example 1, except that in Comparative Example 5, the titanium dioxide particles obtained after the first calcination and screening (step 3) are directly subjected to a second calcination without ultrasonic cleaning.

[0107] Example 1: Characterization Test of Titanium Dioxide Adsorbent Particulate Material

[0108] The modified titanium dioxide particles prepared in Example 1 were characterized by XRD, SEM, etc. Figure 1 X-ray diffraction (XRD) patterns of the modified TiO2 particles indicate that the self-made modified TiO2 particles are anatase phase. Figure 2 Scanning electron microscope (SEM) images show that the prepared modified TiO2 particles are smooth, free of fragmented microparticles, with particle sizes ranging from 50 to 180 μm, mainly concentrated around 100 μm. Further magnification reveals... Figure 3It can be seen that the surface of the granular material is smooth and dense, with a relatively regular overall shape and no microparticles adhering to the surface. Figure 4 It can be seen that the particulate material is composed of aggregated titanium dioxide nanoparticles, with a size range of 10-100 nm, mainly concentrated in the 20-70 nm range. The surface is smooth and regular with minimal defects. BET specific surface area: 78 m² 2 / g, pore size 5-30 nm.

[0109] Experimental Example 2: Adsorbent Performance Test.

[0110] (1) 2mCi level 68 Ge- 68 Ga generator performance test

[0111] The adsorbent materials prepared in Examples 1-5 and Comparative Examples 3-5 were assembled with generator pipes, connectors, lead shielding, shells, and other accessories to form a cold generator, and then loaded with... 68 Ge nuclide preparation of 2mCi 68 Ge- 68 Ga generators were tested and their performance indicators were examined by rinsing. Based on the test results, suitable generators were selected. 68 Ge- 68 The material of the Ga generator adsorbent was used. The generator was rinsed with 2 mL of 0.1 M hydrochloric acid solution. The rinsing efficiency and... 68 The results of Ge breakdown are shown in the table below.

[0112] Table 1

[0113] .

[0114] Results Analysis: As shown in Table 1, the 2mCi adsorbents prepared using the adsorbents in Examples 1-5 68 Ge- 68 Ga generator 68 The Ge leakage rate is ≤0.0001%, which meets the requirements. 68 Ge- 68 Basic performance and quality requirements for Ga generators, which can be used for 68 Ge- 68 Commercial development of Ga generators. It can be seen that, compared with existing technologies... 68 Ge- 68 Compared to the performance of a Ga generator, a 2mCi... 68 Ge- 68 The initial rinsing efficiency of the Ga generator remains consistent with existing technologies. This is because... 68 Ge- 68 The rinsing efficiency of Ga generator and 68 The activity of Ge loading is related to this; within the range of 2-30 mCi, due to... 68Ge loading has low activity and is in an unsaturated state, so the rinsing efficiency is not noticeably different or the improvement is not significant. 68 The significantly reduced Ge leakage rate indicates that the titanium dioxide prepared using the method described in this application exhibits a significant performance improvement compared to existing technologies. On the other hand, the preparation methods of Comparative Example 1 (replacing the inhibitor with ammonia) or Comparative Example 2 (without secondary gelation) failed to produce micron-sized titanium dioxide or yielded too low a result, while the adsorbents prepared in Comparative Examples 3, 4, and 5 were used for… 68 Ge- 68 The Ga generator has poor performance, resulting in low rinsing efficiency, and 68 Ge leakage is far higher than 0.001%, making it unsuitable for commercial development. This indicates that when preparing titanium dioxide using the sol-gel method, the inhibitor must be specifically glacial acetic acid, and calcination and washing must be performed in a secondary gel state, with precise control of the calcination temperature and time, to obtain titanium dioxide nanoparticles with a particle size of 10-300 μm, a size range of 10-100 nm, a pore size of 5-30 nm, and a specific surface area of ​​30-100 m². 2 / g, and with a smooth surface, exhibiting anatase phase, titanium dioxide is necessary to improve the adsorption capacity when used as an adsorbent. 68 Ge- 68 Performance of Ga generator.

[0115] Furthermore, based on Experimental Example 2-(1), the titanium dioxide prepared in Comparative Examples 1-5 does not have commercial development prospects, while the performance of the titanium dioxide adsorbents prepared in Examples 1-5 is not significantly different. Therefore, subsequent experiments will compare Example 1 with the existing technology.

[0116] (2) 30~85mCi 68 Ge- 68 Ga generator performance test

[0117] The 30–85 mCi loading activity is the most common loading range in commercially available products; therefore, this experiment focuses on the 30–85 mCi activity range. 68 Ge- 68 Ga generators and existing commercially available 68 Ge- 68 A comparative analysis was conducted on Ga generators. The adsorbent material prepared in Example 1 was used to assemble a cold generator with generator piping, connectors, lead shielding, and housing components, and then loaded... 68 Ge nuclides were prepared at concentrations of 30 mCi, 50 mCi, and 85 mCi. 68 Ge- 68 The Ga generator was rinsed, and its performance was evaluated. The generator was rinsed with 5 mL of 0.1 M hydrochloric acid solution. The rinsing efficiency and [other parameters] were measured. 68The results of Ge breakdown are shown in the table below.

[0118] Experimental results: 30~85mCi 68 Ge- 68 The performance test results of the Ga generator are shown in Table 2. 68 Ga rinsing efficiency), Table 3 ( 68 Ge breakdown rate), common commercial products 68 Ge- 68 The performance of the Ga generator is shown in Table 4. Figure 5 50 mCi 68 Ge- 68 The graph shows the variation of the Ga generator rinsing efficiency and the linear fitting results.

[0119] Results Analysis: Tables 2 and 3 show that within the loading activity range of 30-85 mCi, the initial rinsing efficiency was above 80%, reaching a maximum of 86%, and the rinsing efficiency remained above 70% even after long-term rinsing (200 days of rinsing time). This is comparable to several commonly available commercially available products. 68 Ge- 68 Compared to Ga generators (Table 4), in 68 While reducing the Ge leakage rate (approximately 0.0001%), the initial leaching efficiency is increased to over 80%, and the leaching efficiency remains above 70% after 200 days of leaching. This demonstrates that the titanium dioxide prepared by the method described in this application can be used for... 68 Ge- 68 The performance of the Ga generator has been greatly improved.

[0120] Table 4. Explanation of Long-Term Rinse Efficiency Time: Current technology does not specify clear requirements for long-term rinsing efficiency, and different manufacturers have different specifications. Commonly published long-term rinsing data is 200 days of rinsing time or 200 rinsing cycles, for pharmaceutical grade. 68 Ge- 68 Ga generators typically have a maximum shelf life of 12 months, and are chemical grade. 68 Ge- 68 Ga generators can last up to 3 years (depending on different performance metrics, such as those from Russia). 68 Ge- 68 Ga generator with a rinsing efficiency of ≥45% 68 (Ge leakage ≤0.005%, validity period up to 3 years). Therefore, this application uses 200 days as the long-term rinsing efficiency comparison time.

[0121] Furthermore, Figure 5 50mCi level 68 Ge- 68The graph showing the change in rinsing efficiency of the Ga generator over 200 days reveals that the rinsing efficiency decreases slowly with increasing rinsing frequency, exhibiting a fluctuating trend. Based on this trend, a linear fitting formula was obtained for the change (y = -2.06 × 10⁻⁶). -4 (x + 0.798), and through calculation, it can be concluded that after 12 months, the rinsing efficiency can still be maintained above 70% (according to the formula, substituting the rinsing days x = 365 into the formula yields y = 72%). Furthermore, multiple rinsing cycles... 68 The leakage rate of Ge remains stable at approximately 0.0001%, far lower than that of gallium chloride in the European Pharmacopoeia. 68 Ga] solution standard pair 68 The leakage rate of Ge is limited to ≤0.001%.

[0122] Table 2

[0123] .

[0124] Table 3

[0125] .

[0126] Table 4

[0127] .

[0128] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for 68 Ge- 68 The method for preparing titanium dioxide adsorbent for Ga generator is characterized by... The adsorbent was prepared using the sol-gel method, including the following steps: The titanium source was dissolved in an organic alcohol and then glacial acetic acid was added to obtain a titanium source solution. The titanium source solution was added dropwise to the purified aqueous solution while stirring, and the mixture was allowed to stand to obtain the first gel. The first gel was then heated and kept warm, and then recrystallized to obtain the second gel. After the second gel is calcined and shaped, it is crushed and screened to obtain solid particles with a particle size of 10-300μm for surface modification in order to remove extremely fine particles on the surface of the solid particles and make the surface smooth. Then, it is calcined a second time to obtain the adsorbent. The first roasting temperature is 300-700℃ and the time is 1-12h; the second roasting temperature is 400-700℃ and the time is 1-6h.

2. The preparation method according to claim 1, characterized in that, The stirring speed for the method of adding dropwise while stirring is 10-100 rpm, and the dropping speed is 1-100 mL / min.

3. The preparation method according to claim 1 or 2, characterized in that, The volume ratio of the titanium source solution to purified water is 1:(0.5-10).

4. The preparation method according to claim 1, characterized in that, The heating and heat preservation temperature is 110-180℃, and the time is 6-36h.

5. The preparation method according to claim 1, characterized in that, Surface modification of solid particles is achieved by ultrasonic treatment, wherein the ultrasonic power is 50-1000W and the time is 0.5-12h.

6. The preparation method according to claim 1, characterized in that, Grind and screen solid particles with particle sizes of 30-60μm, 50-100μm, 75-150μm, and 90-180μm.

7. A titanium dioxide adsorbent prepared according to any one of claims 1-6.

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