CN117258540A

CN117258540A - Germanium [ 68 Ge]Gallium [ 68 Ga]Generator(s)

Info

Publication number: CN117258540A
Application number: CN202311178638.XA
Authority: CN
Inventors: 胡晓阳; 张双; 胡仁鑫; 蒋登荣; 吴洁; 谭文静; 柳芳; 葛强; 蔡继鸣
Original assignee: Chengdu Nurit Medical Technology Co ltd
Current assignee: Chengdu Nurit Medical Technology Co ltd
Priority date: 2023-09-13
Filing date: 2023-09-13
Publication date: 2023-12-22

Abstract

The present invention relates to a kind of ⁶⁸ Ge‑ ⁶⁸ Ga generator belongs to radioactive material application field. The present invention is directed to the prior art ⁶⁸ Ge‑ ⁶⁸ In Ga generator ⁶⁸ The Ga leaching efficiency is limited, and the leaching efficiency after leaching for many times is obviously reduced, provides a method for leaching ⁶⁸ Ge‑ ⁶⁸ Ga generator composed of 10-100nm nanoparticles with specific surface area of 30-100m by loading particles with size of 10-300 μm ² Titanium dioxide particles with a pore size of 5-30nm and a smooth surface and an anatase phase, are prepared ⁶⁸ Ge‑ ⁶⁸ Ga generator, above the activity range of 30mCi, ⁶⁸ the Ge leakage rate was reduced to about 0.0001%, initial ⁶⁸ The Ga leaching efficiency is improved to be more than 75%, and the leaching efficiency can be kept to be more than 70% for a plurality of times.

Description

Germanium [ 68 Ge]Gallium [ 68 Ga]Generator(s)

Technical Field

The invention relates to a germanium [ ⁶⁸ Ge]Gallium [ ⁶⁸ Ga]A generator, which belongs to the application field of radioactive materials.

Background

Germanium [ ⁶⁸ Ge]Gallium [ ⁶⁸ Ga]Generator [ ] ⁶⁸ Ge- ⁶⁸ Ga generator) is ⁶⁸ One source of great importance is the Ga species, ⁶⁸ Ge- ⁶⁸ the Ga generator is small in size, convenient to transport, free of large-scale equipment such as an accelerator, relatively low in price, capable of being used at any time and being used at any time, and widely applicable to multiple occasions such as hospitals and research institutions. At present, there are a plurality of types ⁶⁸ Ge- ⁶⁸ Ga generators are marketed. It generally uses inorganic adsorption material or organic molecule as adsorbent, such as tin dioxide (SnO) ₂ ) Titanium dioxide (TiO) ₂ ) Tantalum oxide (Ta) ₂ O ₅ ）、SiO ₂ Organic copolymers, etc., in addition, other adsorbent materials such as glass microspheres, zirconia (ZrO ₂ ) Cerium oxide (CeO) ₂ ) There are many researches and reports that the separation mechanism is based on the adsorption of only parent nuclides by solid-phase adsorption materials ⁶⁸ Ge, and a daughter nuclide ⁶⁸ The principle that Ga is hardly adsorbed, the chromatographic column is periodically leached by hydrochloric acid solution ⁶⁸ Ga slave ⁶⁸ Ge was separated. Wherein, to ⁶⁸ Leakage rate and pair of Ge ⁶⁸ The elution efficiency of Ga and the stability of the elution efficiency under long-term elution were evaluated ⁶⁸ Ge- ⁶⁸ Important indicators of Ga generator performance.

⁶⁸ The leak rate of Ge was evaluated during rinsing ⁶⁸ The Ge is eluted out of the column index, ⁶⁸ the higher the leak rate of Ge, the separated ⁶⁸ The lower the purity of Ga, the current European pharmacopoeia gallium chloride [ ⁶⁸ Ga]Solution standard pair ⁶⁸ The leak penetration rate of Ge is limited to be less than or equal to 0.001%; while ⁶⁸ The elution efficiency of Ga is evaluated in elution ⁶⁸ The index of the chromatographic column in which Ga is eluted, ⁶⁸ the higher the leaching efficiency of Ga, the more ⁶⁸ The more Ga, and therefore, in actual production, the higher ⁶⁸ Ga leaching efficiency and lower ⁶⁸ The leakage rate of Ge tends to mean better ⁶⁸ Ge- ⁶⁸ Ga generator performance.

In 1996, russian cyclotron corporation was first offering modified TiO-based to the market ₂ Of materials ⁶⁸ Ge- ⁶⁸ The Ga generator has an initial leaching efficiency of 60-75%, ⁶⁸ ge leakage rate about 0.001% (Journal of Nuclear Medicine and Molecular Imaging, 2019, 9, 30-66); in recent years, eckert, germany&TiO-based was also developed successively by Ziegler, IRE EliT, belgium, etc ₂ Commercialization of materials ⁶⁸ Ge- ⁶⁸ Ga generators, however, have a gradually decreasing leaching efficiency with increasing use time, even down to below 55%; U.S. patent No. 3,262B 2 also discloses a method for preparing a chromatographic adsorption material for a nuclide generator, from which 33 mCi-grade is prepared ⁶⁸ Ge- ⁶⁸ Ga generator, for ⁶⁸ The initial leaching efficiency of Ga is about 75%, the leaching efficiency of repeated leaching can be stabilized at more than 65%, ⁶⁸ the Ge leakage rate can meet the European pharmacopoeia gallium chloride ⁶⁸ Ga]The standard of the solution is less than or equal to 0.001 percent.

It can be seen that the prior art discloses ⁶⁸ Ge- ⁶⁸ Ga generator pair ⁶⁸ The leaching efficiency of Ga is generally not higher than 75% because of the pharmaceutical grade ⁶⁸ Ge- ⁶⁸ Ga generator is required to satisfy at least 0.001% or less ⁶⁸ The Ge leakage rate is improved ⁶⁸ The leaching efficiency of Ga is often accompanied by ⁶⁸ The leak rate of Ge is correspondingly improved, resulting in ⁶⁸ The leaching efficiency of Ga is limited.

Based on the aboveThere remains a need in the art for an analysis with lower levels of performance ⁶⁸ Ge leakage and higher and more stable ⁶⁸ Efficiency of Ga leaching ⁶⁸ Ge- ⁶⁸ Ga generator.

Disclosure of Invention

Based on the above problems, an object of the present invention is to provide a device ⁶⁸ Ge- ⁶⁸ Ga generator, which is loaded with adsorbent having excellent and stable performance, so that ⁶⁸ Ge- ⁶⁸ During operation of the Ga generator ⁶⁸ The Ge leakage rate is less than or equal to 0.0001 percent, the activity range is more than 30mCi level, and the initial process is carried out ⁶⁸ The Ga leaching efficiency is improved to be more than 75%, and the leaching efficiency of leaching for multiple times can be kept to be more than 70%.

Based on the above object, the technical scheme of the invention provides a method for manufacturing a semiconductor device ⁶⁸ Ge- ⁶⁸ Ga generator, comprising a packing cylinder for packing adsorbent, the adsorbent is specifically adsorbed with ⁶⁸ Ge；

Wherein the adsorbent has a particle size of 10-300 μm, and is composed of 10-100nm nanoparticles with a specific surface area of 30-100m ² And/g, the pore diameter is 5-30nm, the surface is smooth, and the granular titanium dioxide is in anatase phase.

Preferably, the titanium dioxide particles have a size of 30-60 μm, 50-100 μm, 75-150 μm, 90-180 μm.

Further, the preparation method of the titanium dioxide is a sol-gel method, and comprises the following steps of

Dissolving a titanium source by using organic alcohol, and then adding glacial acetic acid to obtain a titanium source solution;

dropwise adding the titanium source solution into the purified water solution while stirring, standing to obtain a first gel, heating and preserving heat, and recrystallizing to obtain a second gel;

and (3) after the second gel is formed by the first roasting, grinding and screening solid particles with the particle size of 10-300 mu m for surface modification, and then obtaining the adsorbent by the second roasting.

Preferably, the addition amount of the titanium source solution and the purified water is 1: (0.5-10) the stirring speed of the dropwise adding mode is 10-100 revolutions per minute while stirring, and the adding speed is 1-100mL per minute.

Preferably, the heating and heat preserving temperature is 110-180 ℃ and the time is 6-36h.

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

Preferably, the first roasting temperature is 300-700 ℃, and the second roasting temperature is 400-700 ℃; the first roasting time is 1-12h, and the second roasting time is 1-6h.

Preferably, the material of the packing cylinder is a plastic chromatographic column, a glass tube, a quartz tube and the like.

Further, the said ⁶⁸ Ge- ⁶⁸ The Ga generator also comprises an elution pipeline and a lead shielding body.

Further, according to the loading ⁶⁸ Different Ge activities, bringing the above ⁶⁸ Ge- ⁶⁸ Ga generators are classified into different classes.

The invention has the following beneficial effects:

the present invention is directed to the prior art ⁶⁸ Ge- ⁶⁸ In Ga generator ⁶⁸ The Ga leaching efficiency is limited, and the leaching efficiency after leaching for many times is obviously reduced, provides a method for leaching ⁶⁸ Ge- ⁶⁸ Ga generator composed of 10-100nm nanoparticles with specific surface area of 30-100m by loading particles with size of 10-300 μm ² Titanium dioxide particles with a pore size of 5-30nm and a smooth surface and an anatase phase, are prepared ⁶⁸ Ge- ⁶⁸ Ga generator, above the activity range of 30mCi, ⁶⁸ the Ge leakage rate was reduced to about 0.0001%, initial ⁶⁸ The Ga leaching efficiency is improved to be more than 75%, and the leaching efficiency can be kept to be more than 70% for a plurality of times.

Drawings

FIG. 1:50mCi ⁶⁸ Ge- ⁶⁸ Elution efficiency change for 200 days in Ga generator and linear fit.

Detailed Description

Embodiments of the present invention will be described in detail below with reference to examples, which will be understood by those skilled in the art, for illustrating the present invention only and should not be construed as limiting the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention. Unless specifically indicated, the amounts listed are based on total weight and are described in parts by weight. The invention should not be construed as being limited to the particular embodiments described.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, if not otherwise defined, to which this invention belongs.

The term "leaching efficiency" refers to when the parent nuclide ⁶⁸ Ge decays to daughter nuclides ⁶⁸ After Ga, the mixture is collected after leaching by a leaching agent ⁶⁸ Ratio of the actual amount of Ga to the theoretical amount.

The term "leakage rate" refers to the rate at which when rinsed by a rinse agent, ⁶⁸ leaching rate of Ge.

The term "specific surface area" refers to the total area per unit mass of the adsorbent material, as measured by gas adsorption.

The term "titanium dioxide particle size" refers to the size of titanium dioxide microparticles, which are aggregated from nanoparticles.

The term "nanoparticulate" refers to nanoparticulate titanium dioxide that aggregate to form microparticles of titanium dioxide.

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

In the context of the present invention, the term "comprising" or "comprises" does not exclude other possible elements. The compositions of the present invention (including embodiments described herein) may comprise, consist of, or consist essentially of the following elements; the essential elements of the invention described herein and any of the other or optional ingredients, components or limitations described herein or otherwise as desired.

Turning now to the present invention in more detail, it should be noted that the various aspects, features, embodiments, examples and advantages thereof described herein may be compatible and/or combinable.

Embodiments of the present application disclose a method of ⁶⁸ Ge- ⁶⁸ Ga generator, comprising a packing cylinder for packing adsorbent, the adsorbent is specifically adsorbed with ⁶⁸ Ge；

The applicant found that the titanium dioxide adsorbent with the performance standard has better adsorption performance and can lead to ⁶⁸ Ge- ⁶⁸ Of Ga generators ⁶⁸ The Ge leakage rate is reduced to about 0.0001 percent, the activity range is above 30-85mCi level, ⁶⁸ the Ga leaching efficiency is improved to be more than 75%, the highest is 86%, and the leaching efficiency of multiple leaching can be kept to be more than 70%.

It is understood that the particle size of the adsorbent as used herein is 10-300 μm, meaning that the particle size of the titanium dioxide is in the range of 10-300. Mu.m, and may be a specific particle size, such as 10 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, or any range of particle size in the range of 10-300. Mu.m, such as 10-50 μm, 30-60 μm, 50-150 μm, 20-200 μm, 130-260 μm, 200-300. Mu.m; preferably 30-60 μm, 50-100 μm, 75-150 μm, 90-180 μm. The specific surface area, nanoparticle size, pore size are as described above, for example, the specific surface area may be 30m ² /g 、40 m ² /g 、70 m ² /g 、85 m ² /g 、100 m ² /g, may also be 30-50 m ² /g 、50-100 m ² /g 、80-100 m ² The specific surface area is in the range of/g; nanoparticle sizes may be in the range of 10nm, 20 nm, 50 nm, 60nm, 80 nm, 100nm, or 10-30, 20-60nm, 50-100 nm; the pore size may be in the range of 5-10 nm, 10-25nm, 20-30 nm, 5-nm, 10nm, 15 nm, 20 nm, 30nm, or 5-10 nm.

In the present practiceIn embodiments, 10-300 μm grade particulate titanium dioxide may be reduced ⁶⁸ The Ge leakage rate and the specific surface area influence the crystal structure, thereby influencing the yield, the aperture and the surface smoothness of the anatase phase of the titanium dioxide ⁶⁸ Ga leaching efficiency; in the case that the titanium dioxide meets the above criteria, the reduction is only possible ⁶⁸ Ge- ⁶⁸ Of Ga generators ⁶⁸ Ge leakage rate and enhancement ⁶⁸ Ga elution efficiency and elution stability.

In this embodiment, the preparation method of the titanium dioxide is a sol-gel method, and includes the following steps: dissolving a titanium source by using organic alcohol, and then adding glacial acetic acid to obtain a titanium source solution; dropwise adding the titanium source solution into the purified water solution while stirring, standing to obtain a first gel, heating and preserving heat, and recrystallizing to obtain a second gel; and (3) after the second gel is formed by the first roasting, grinding and screening solid particles with the particle size of 10-300 mu m for surface modification, and then obtaining the adsorbent by the second roasting.

In the embodiment, the specific preparation method of the titanium source solution is a conventional sol-gel method, namely, dissolving a titanium source (such as tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate and the like) by using an organic alcohol solution, and then adding an inhibitor (such as glacial acetic acid and the like) to inhibit hydrolysis of the titanium source solution to form the titanium source solution; the present application is not particularly limited, but provides only preferred embodiments.

In a preferred embodiment, the method for preparing the titanium source solution comprises the following steps:

s1, dissolving titanium source (such as tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate, tetrahexyl titanate and the like) in C ₂ -C ₅ And (3) in the alcohol solution, uniformly mixing to obtain a clear and transparent solution. The purpose of this step is to dissolve the titanium source. Wherein, the titanium source is connected with C ₂ -C ₅ The volume ratio range of the alcohol solution is preferably 2: (0.5-20), more preferably tetraisopropyl titanate, tetrabutyl titanate, more preferably isopropyl alcohol in the alcohol solution, and when isopropyl alcohol is in the alcohol solution, more preferably 1: (3-6).

S2, dropwise adding the obtained clear and transparent solution into glacial acetic acid while stirring to obtain a white turbid solution, and standing for a period of time to obtain the clear and transparent solution, namely the titanium source solution. The purpose of this step is to inhibit hydrolysis of the titanium source. Wherein, the volume ratio range of the titanium source and the glacial acetic acid is preferably 1: (0.5-10), more preferably 1:1.

The prior art generally adopts sulfuric acid method, chloridizing method and the like to prepare titanium dioxide, and has the advantages of complex process, high energy consumption, more wastes, high metal impurity content and complex crystal form of the prepared titanium dioxide, and can not be used as ⁶⁸ Ge- ⁶⁸ The Ga generator adsorbs the filler; US10357758B2 discloses a method for ⁶⁸ Ge- ⁶⁸ The initial adsorption efficiency of the Ga generator for adsorbing the titanium dioxide of the filler is 75%, the leaching efficiency of long-term leaching is stabilized at about 65%, and the data disclosed in the prior art can be found that the method satisfies the following conditions ⁶⁸ The leakage rate of Ge accords with European pharmacopoeia for gallium chloride ⁶⁸ Ga]Under the precondition of the standard (less than or equal to 0.001%) of the solution, ⁶⁸ the leaching efficiency of Ga is generally not higher than 75%, and the leaching efficiency is obviously reduced after leaching for many times. The sol-gel method is simple, quick and environment-friendly, and does not have the risk of introducing other metal ions, so that the sol-gel method becomes a focus of attention of technicians. However, the titanium dioxide prepared by the sol-gel method of the prior art is generally nano-scale, because the titanium source is aggregated in purified water to form sol particles of about 1nm after the titanium source solution is formed by the action of organic alcohol and inhibitor, the sol particles further grow to form gel in the standing process, but the gel is only the lap joint among the sol particles and is still nano-scale titanium dioxide hydrate essentially, therefore, more than 80 percent of the nano-scale titanium dioxide is obtained after the gel is directly dried, roasted and crushed, and the titanium dioxide is easy to excessively press the chromatographic column after the filling of the chromatographic column due to the small particle size, the elution loss rate is increased and ⁶⁸ ge leakage rate; in the case of glacial acetic acid as inhibitor, although a part of the micron-sized titanium dioxide particles (the nano-sized titanium dioxide is formed by aggregation) can also be obtained by screening, the yield is generally lower than 20%, the yield is unstable, and at the same time, the adsorption performance of the micron-sized titanium dioxide particlesAnd the leakage rate can not meet the requirement.

In view of this, the present application performed a secondary gelation in the titanium source gelation stage, and the first gel was heated and incubated to recrystallize, thereby aggregating the nanosize sol particles to grow into a first gel, and after the secondary heating and incubation, the particle size of the sol particles was aggregated to form a second gel, thereby allowing the calcined and ground titanium dioxide to exist in the micrometer-sized particle size.

In order to achieve the micron-sized particle size of the titanium dioxide, the inhibitor for preparing the titanium source solution is limited to glacial acetic acid; the inhibitors in the prior art generally comprise glacial acetic acid, ethanolamine, ammonia water, acetylacetone and the like, but the applicant finds that even if other inhibitors are added and subjected to secondary gel, micron-sized titanium dioxide meeting the requirements cannot be obtained through screening, and the requirements can be met only when the inhibitor is glacial acetic acid.

However, the applicant further found that on the premise that the inhibitor is glacial acetic acid, the leakage rate and the leaching efficiency of the micron-sized titanium dioxide screened out after primary roasting are not ideal regardless of the primary gel or the secondary gel.

The micron-sized titanium dioxide obtained by primary roasting is obtained by further aggregating the nano-sized titanium dioxide in secondary gel, and under the condition of primary roasting, the nano-sized titanium dioxide grains aggregated to form the micron-sized titanium dioxide are too small, so that the specific surface area of the material is too large, the surface active sites are too many, the adsorption capacity of the material to germanium and gallium is high, and the separation effect is difficult to achieve; on the other hand, the titanium dioxide obtained after the primary roasting has more extremely fine particles adhered to the surface, which causes the surface roughness of the crystal grains and the increase of the specific surface area, and the extremely fine particles are not firmly adhered and are washed out with the leaching agent during the leaching, resulting in ⁶⁸ The Ge leakage is greatly increased, and the influence is affected ⁶⁸ Ga leaching efficiency and stability after multiple leaches.

In view of the above problems, the applicant has found that titanium dioxide particles having a size of 10 to 300 μm and composed of nano-sized titanium dioxide particles in the range of 10 to 100nm, have a specific surface area, under the premise of forming micro-sized titanium dioxideIs 30-100m ² Per g, pore diameter of 5-30nm, smooth surface, anatase phase, and its use as ⁶⁸ Ge- ⁶⁸ The performance of the adsorbent of the Ga generator is greatly enhanced.

Based on the above, the titanium dioxide obtained after the first roasting is subjected to surface modification, so that the surface of titanium dioxide particles is smooth, and meanwhile, ultrafine particles on the surface are removed; then the secondary roasting is carried out, and the nano-scale titanium dioxide particles which are aggregated to form the micro-scale titanium dioxide in the obtained micro-scale titanium dioxide have the size range of 10-100nm, the aperture of the nano-scale titanium dioxide is 5-30nm, and the specific surface area is 30-100m ² /g, and has a smooth surface, in anatase phase, the titanium dioxide being used for ⁶⁸ Ge- ⁶⁸ Ga generator adsorbent, in different cases ⁶⁸ Under Ge loading activity ⁶⁸ The Ge leakage rate was reduced to about 0.0001% for the initial ⁶⁸ The Ga leaching efficiency is improved to be more than 75%, and the leaching efficiency can be kept to be more than 70% for a plurality of times.

In the above embodiment, the nano-titania particles which are aggregated to form the micro-scale titania are controlled to have a size ranging from 10 to 100nm because the nano-titania particles in this size range contain a large number of grain boundaries which can eliminate crystal defects, are more resistant to radiation and improve the performance of the micro-scale titania as compared with the crystal grains having a size ranging from more than 100nm, but the above-mentioned titania is resistant to ⁶⁸ Ge and Ge ⁶⁸ Ga has adsorption capacity, so that the pore diameter of nano-level titanium dioxide needs to be controlled to be 5-30nm, and the specific surface area is 30-100m ² /g, increase pair ⁶⁸ Ge and Ge ⁶⁸ Adsorption selectivity of Ga, so that the titanium dioxide adsorbent is improved in pair ⁶⁸ Adsorption capacity of Ge and minimizing the adsorption to Ge ⁶⁸ Adsorption of Ga, thus shows ⁶⁸ Increase in Ga leaching efficiency and ⁶⁸ and the Ge leakage rate is reduced.

Thus, the prepared titanium dioxide adsorbent accords with the particle size of 10-300 mu m, consists of 10-100nm titanium dioxide nano particles and has the specific surface area of 30-100m ² Per g, pore size of 5-30nm, smooth surface, anatase phase standard, and the titanium dioxide is used as ⁶⁸ Ge- ⁶⁸ The adsorbent of Ga generator is different in that ⁶⁸ Under Ge loading activity ⁶⁸ The Ge leakage rate was reduced to about 0.0001% for the initial ⁶⁸ The Ga leaching efficiency is improved to be more than 75%, and the leaching efficiency can be kept to be more than 70% for a plurality of times (within a leaching period of 200 days).

In a further embodiment, the titanium source solution is added dropwise to the purified aqueous solution while stirring in the titanium source gelation step, the stirring speed being controlled to be 10 to 100 rpm, and the dropping speed being 1 to 100mL/min. This is because the stirring speed and the dropping time have a certain influence on the particle diameter of the sol particles, and reasonable control of the stirring speed and the dropping time is advantageous to increase the particle diameter of the sol particles forming the first gel, thereby shortening the time for the sol particles to grow from the nano-scale to the micro-scale when forming the second gel, and increasing the amount of the titanium dioxide having the micro-scale particle diameter after grinding. In this embodiment, the amount of titanium source solution added to the purified water can be routinely selected by those skilled in the art, and is preferably 1: (0.5-10) volume ratio.

In a further embodiment, the heating and incubation temperature at which the second gel is formed is 110-180 ℃ for a period of 6-36 hours. The temperature and time of the heat soak affects the rate and size of growth of the sol particles from the nano-scale to the micro-scale, and those skilled in the art, after learning the technical principles of the present application, can routinely choose the size of the sol particles to be obtained. However, in the present application, since more titanium dioxide of 10 to 300 μm is required, the holding temperature is preferably 110 to 180℃and the holding time is preferably 6 to 36 hours.

In a further embodiment, the purpose of the surface modification is to obtain a smooth surface, and at the same time remove the ultrafine particulate titanium dioxide on the surface, which can be performed by means of vibration, vortex, ultrasound, etc., and the application is preferably ultrasound, the power of the ultrasound is 50-1000W, and the time is 0.5-12 h.

In a preferred embodiment, the grinding and screening solid particles having a particle size of 30-60 μm, 50-100 μm, 75-150 μm, 90-180 μm; the applicant has found that the combination of the above particle sizes further enhances the performance of the titanium dioxide as an adsorbent.

In a further embodiment, the first firing temperature is 300-700 ℃ and the second firing temperature is 400-700 ℃. The applicant has found that the firing temperature and firing time affect the specific surface area of the titanium dioxide. The roasting temperature can obtain 30-100m to the maximum extent ² Titanium dioxide of specific surface area/g; the roasting time is preferably 1-12h for the first roasting time and 1-6h for the second roasting time.

It will be appreciated that after formation of the second gel, in order to remove the residual solvent on the gel surface, the step of further heating the second gel in an oven to remove the residual solvent, preferably at a temperature of 110-180 c, is also included as disclosed in conventional sol-gel methods, the purpose of which is to remove the residual organic alcohols and glacial acetic acid on the surface.

It will be appreciated that the surface modification requires placing the solid particles in an aqueous solution of purified water to facilitate removal of very fine particles by shaking and smoothing the surface, and that purified water may be conventionally replaced by 0.1mol/L hydrochloric acid solution for enhanced effect, while drying to surface drying is required after surface modification, preferably at a temperature of 110-180 ℃.

In some preferred embodiments, the packing cylinder is made of plastic chromatographic columns, glass tubes, quartz tubes, etc.

In some preferred embodiments, the ⁶⁸ Ge- ⁶⁸ The Ga generator also comprises an elution pipeline and a lead shielding body.

In some preferred embodiments, according to the loading ⁶⁸ Different Ge activities, bringing the above ⁶⁸ Ge- ⁶⁸ Ga generators are classified into different classes. For example, according to the loading ⁶⁸ The Ge activities are different, 30mCi grade, 50mCi grade and 80 mCi grade can be obtained ⁶⁸ Ge- ⁶⁸ Ga generator.

It should be noted that the above loading activities are only preferred loading activities in the present application, and should not be construed as limiting the loading activities, and the titanium dioxide prepared in the present application may be prepared into different loading activities such as micro curie level, millicurie level, hundred millicurie level, etc. due to excellent properties ⁶⁸ Ge- ⁶⁸ GaA generator.

The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the detailed description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the invention.

Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.

Example 1 preparation of titania adsorbent

1. Dropwise adding 50mL of tetrabutyl titanate into 200mL of isopropanol, and uniformly mixing to obtain a clear and transparent solution; dropwise adding 50mL of glacial acetic acid into the clear and transparent solution, and standing at room temperature for 24 hours to obtain a titanium source solution;

2. dropwise adding the titanium source solution into 200mL of purified water at a stirring speed of 55 rpm and a dropwise adding speed of 5mL/min while stirring, standing at room temperature for 24h to convert the solution into first gel, and heating the first gel in an air circulation oven to 150 ℃ for 24h to obtain second gel;

3. and (3) placing the second gel in a muffle furnace, heating to 400 ℃ at a heating rate of 5 ℃/min, roasting for 4 hours, and naturally cooling at room temperature. Taking out, grinding in a mortar, screening by a screen, and screening solid particles within a range of 50-180 mu m;

4. placing the screened solid particles into 0.1M HCl solution, carrying out ultrasonic treatment for 2 hours, rinsing to remove ultrafine particles with ultrasonic power of 200w, washing for many times, then placing into a drying oven for drying at 150 ℃, placing the dried solid particles into a muffle furnace, heating to 500 ℃ at a heating rate of 5 ℃/min, roasting for 3 hours, naturally cooling at room temperature, and taking out to obtain the titanium dioxide adsorbent.

EXAMPLE 2 preparation of Titania adsorbent

1. Dropwise adding 50mL of tetrabutyl titanate into 200mL of absolute ethyl alcohol, and uniformly mixing to obtain a clear and transparent solution; dropwise adding 50mL of glacial acetic acid into the clear and transparent solution, and standing at room temperature for 24 hours to obtain a titanium source solution;

2. dropwise adding the titanium source solution into 1500mL of purified water at a stirring speed of 10 revolutions per minute and a dropwise adding speed of 50mL/min while stirring, standing at room temperature for 24 hours to convert the titanium source solution into first gel, and heating the first gel in an air circulation oven to 110 ℃ for 26 hours to obtain second gel;

3. and (3) placing the second gel in a muffle furnace, heating to 300 ℃ at a heating rate of 5 ℃/min, roasting for 1h, and naturally cooling at room temperature. Taking out, grinding in a mortar, screening by a screen, and screening solid particles within a range of 10-300 mu m;

4. placing the screened solid particles into 0.1M HCl solution, carrying out ultrasonic treatment for 6 hours, rinsing to remove ultrafine particles with ultrasonic power of 50w, washing for many times, then placing into a drying oven for drying at 150 ℃, placing the dried solid particles into a muffle furnace, heating to 400 ℃ at a heating rate of 5 ℃/min, roasting for 1 hour, naturally cooling at room temperature, and taking out to obtain the titanium dioxide adsorbent.

EXAMPLE 3 preparation of Titania adsorbent

1. Dropwise adding 50mL of tetrabutyl titanate into 200mL of n-butanol, and uniformly mixing to obtain a clear and transparent solution; dropwise adding 50mL of glacial acetic acid into the clear and transparent solution, and standing at room temperature for 24 hours to obtain a titanium source solution;

2. dropwise adding the titanium source solution into 3000mL of purified water at a stirring speed of 100 revolutions per minute and a dropwise adding speed of 100 mL/minute while stirring, standing at room temperature for 24 hours to convert the titanium source solution into first gel, and heating the first gel in an air circulation oven to 180 ℃ for 36 hours to obtain second gel;

3. and (3) placing the second gel in a muffle furnace, heating to 700 ℃ at a heating rate of 5 ℃/min, roasting for 12 hours, and naturally cooling at room temperature. Taking out, grinding in a mortar, sieving with a mesh screen, and sieving solid particles within the range of 75-150 μm;

4. placing the screened solid particles into 0.1M HCl solution, carrying out ultrasonic treatment for 12 hours, wherein the ultrasonic power is 1000w, rinsing to remove ultrafine particles, washing for many times, then placing into a drying oven for drying, placing the dried solid particles into a muffle furnace, heating to 700 ℃ at a heating rate of 5 ℃/min, roasting for 6 hours, naturally cooling at room temperature, and taking out to obtain the titanium dioxide adsorbent.

EXAMPLE 4 preparation of Titania adsorbent

1. Dropwise adding 50mL of tetrabutyl titanate into 200mL of isoamyl alcohol, and uniformly mixing to obtain a clear and transparent solution; dropwise adding 50mL of glacial acetic acid into the clear and transparent solution, and standing at room temperature for 24 hours to obtain a titanium source solution;

2. dropwise adding the titanium source solution into 800mL of purified water at a stirring speed of 80 revolutions per minute and a dropwise adding speed of 20mL/min while stirring, standing at room temperature for 24 hours to convert the solution into first gel, and heating the first gel in an air circulation oven to 165 ℃ and preserving heat for 35 hours to obtain second gel;

3. and (3) placing the second gel in a muffle furnace, heating to 550 ℃ at a heating rate of 5 ℃/min, roasting for 4.5 hours, and naturally cooling at room temperature. Taking out, grinding in a mortar, screening by a screen, and screening solid particles within a range of 50-100 mu m;

4. placing the screened solid particles into 0.1M HCl solution, carrying out ultrasonic treatment for 8 hours, wherein the ultrasonic power is 120w, rinsing to remove ultrafine particles, washing for many times, then placing into a drying oven for drying, placing the dried solid particles into a muffle furnace, heating to 550 ℃ at a heating rate of 5 ℃/min, roasting for 2 hours, naturally cooling at room temperature, and taking out to obtain the titanium dioxide adsorbent.

EXAMPLE 5 preparation of Titania adsorbent

2. dropwise adding the titanium source solution into 2200mL of purified water at a stirring speed of 30 revolutions per minute and a dropwise adding speed of 70mL/min while stirring, standing at room temperature for 24 hours to convert the titanium source solution into first gel, and heating the first gel in an air circulation oven to 170 ℃ for 30 hours to obtain second gel;

3. and (3) placing the second gel in a muffle furnace, heating to 600 ℃ at a heating rate of 5 ℃/min, roasting for 8 hours, and naturally cooling at room temperature. Taking out, grinding in a mortar, screening by a screen, and screening solid particles in the range of 90-180 mu m;

4. placing the screened solid particles into 0.1M HCl solution, carrying out ultrasonic treatment for 1h, rinsing to remove ultrafine particles with ultrasonic power of 800w, washing for many times, then placing into a drying oven for drying at 150 ℃, placing the dried solid particles into a muffle furnace, heating to 650 ℃ at a heating rate of 5 ℃/min, roasting for 5h, naturally cooling at room temperature, and taking out to obtain the titanium dioxide adsorbent.

Comparative example 1 preparation of titania adsorbent

The preparation is carried out by adopting a sol-gel method in the prior art, wherein the inhibitor is ammonia water (30%), and specifically comprises the following steps:

1. dripping 50mL of tetraisopropyl titanate into 200mL of isopropanol, and uniformly mixing to obtain a clear and transparent solution;

2. dropwise adding ammonia water (30%) into the clear and transparent solution while stirring to adjust the pH to be more than or equal to 7, and standing at room temperature for 24 hours to obtain a titanium source solution;

3. the titanium source solution was added dropwise to 200mL of purified water with stirring, left at room temperature for 24 hours to convert to a first gel, and the gel was subjected to rotary evaporation on a rotary evaporator at 90 ℃ to remove the solvent.

4. And (3) placing the first gel in a muffle furnace, heating to 400 ℃ at a heating rate of 5 ℃/min, roasting for 4 hours, and naturally cooling at room temperature. Taking out, grinding in a mortar, and sieving to obtain yellowish white solid powder.

Mesh screen results: comparative example 1 titanium dioxide prepared by a conventional sol-gel method, and the inhibitor is limited to ammonia water (30%), titanium dioxide particles with a relatively dense range of 10-300 μm cannot be screened out after grinding, and the titanium dioxide cannot be used for adsorbing fillers of nuclides generators.

Comparative example 2 preparation of titania adsorbent

The preparation is carried out by adopting a sol-gel method in the prior art, wherein the inhibitor is glacial acetic acid, and the specific steps are as follows:

2. dropwise adding 50mL of glacial acetic acid into the clear and transparent solution while stirring, and standing at room temperature for 24 hours to obtain a titanium source solution;

4. And (3) placing the first gel in a muffle furnace, heating to 400 ℃ at a heating rate of 5 ℃/min, roasting for 4 hours, and naturally cooling at room temperature. Taking out, grinding in a mortar, and sieving to obtain black or yellowish white solid powder.

Mesh screen results: comparative example 2 titanium dioxide prepared by conventional sol-gel method, and the inhibitor is limited to glacial acetic acid, the crushed titanium dioxide particles with a size ranging from 10 to 300 μm are obtained in a yield of 18%, the yield is too low and the impurities are more, so that the titanium dioxide is difficult to be used as ⁶⁸ Ge- ⁶⁸ Ga generator adsorbent.

Comparative example 3 preparation of titania adsorbent

The preparation method was the same as in example 1, except that the titanium dioxide particles obtained by screening (step 3) after the first calcination were used as they are in comparative example 3 without performing the step 4 process.

Comparative example 4 preparation of titania adsorbent

The preparation method is the same as in example 1, except that the titanium dioxide particles after ultrasonic cleaning and drying in step 4 are directly used in comparative example 4, and the subsequent secondary roasting process is not performed.

Comparative example 5 preparation of titania adsorbent

The preparation method is the same as in example 1, except that the titanium dioxide particles obtained by screening (step 3) after the first firing are directly subjected to the second firing in comparative example 5 without performing the ultrasonic cleaning process.

EXAMPLE 6 preparation of 2mCi grade ⁶⁸ Ge- ⁶⁸ Ga generator

Firstly, weighing 5g of the adsorbent prepared in examples 1-5 and comparative examples 3-5, placing the adsorbent in a glass tube with a sand core, adding glass wool and a sieve plate, compacting, assembling into a generator cold column, and flushing the cold column by 250mL of 0.1M hydrochloric acid solution. And then TiO ₂ The cold leg is placed in the lead shield and the lead shield, generator housing and fittings are assembled to form the cold generator. Taking 2mCi ⁶⁸ Placing Ge solution into penicillin bottle, injecting by syringe positive pressure injection ⁶⁸ Injecting Ge solution into cold generator, continuously injecting air, evacuating residual liquid in column, slowly eluting column with 250mL 0.1M hydrochloric acid solution, injecting air, evacuating residual liquid in column to obtain 2mCi grade ⁶⁸ Ge- ⁶⁸ Ga generator.

EXAMPLE 7 preparation 30Above mCi level ⁶⁸ Ge- ⁶⁸ Ga generator

Firstly, 5g of the adsorbent prepared in the example 1 is weighed and placed in a glass tube with a sand core, glass wool and a sieve plate are added for compaction, a generator cold column is assembled, and 250mL of 0.1M hydrochloric acid solution is used for flushing the cold column. And then TiO ₂ The cold leg is placed in the lead shield and the lead shield, generator housing and fittings are assembled to form the cold generator. Taking 30-85mCi ⁶⁸ Placing Ge solution into penicillin bottle, injecting by syringe positive pressure injection ⁶⁸ Injecting Ge solution into cold generator, continuously injecting air under pressure, evacuating the residual liquid in column, slowly eluting column with 250mL 0.1M hydrochloric acid solution, injecting air under pressure, evacuating the residual liquid in column to obtain 30mCi, 50mCi, and 85mCi respectively ⁶⁸ Ge- ⁶⁸ Ga generator and long-term eluting to examine the relative performance index.

Test example 1 grade 2mCi ⁶⁸ Ge- ⁶⁸ Performance investigation of Ga generator

⁶⁸ Ge- ⁶⁸ Leaching by a Ga generator: taking 2mL of 0.1M hydrochloric acid solution into a 10mL sterile syringe, slowly leaching the generator by means of positive pressure injection, pressurizing and injecting residual liquid in an air evacuation column, collecting leaching solution into a sterile penicillin bottle to obtain gallium chloride [ ⁶⁸ Ga]A solution. Measuring the activity of the leaching solution to obtain a grade of 2mCi ⁶⁸ Ge- ⁶⁸ The leaching efficiency of the Ga generator, ⁶⁸ Ge leak rate and leaching efficiency of multiple leaching.

Test example 2 30mCi grade or more ⁶⁸ Ge- ⁶⁸ Performance investigation of Ga generator

⁶⁸ Ge- ⁶⁸ Leaching by a Ga generator: slowly eluting the generator by adding 5mL of 0.1M hydrochloric acid solution into 10mL of sterile syringe, pressurizing and injecting air to empty the column, collecting the eluate into sterile penicillin bottle to obtain gallium chloride ⁶⁸ Ga]A solution. Measuring the activity of the leaching solution to obtain the activities of 30mCi, 50mCi and 85mCi ⁶⁸ Ge- ⁶⁸ The leaching efficiency of the Ga generator, ⁶⁸ Ge leak rate and leaching efficiency of multiple leaching.

Experimental results:

TABLE 1 grade 2mCi in EXAMPLE 6 ⁶⁸ Ge- ⁶⁸ Ga generator performance test;

TABLE 2 30mCi class or more in EXAMPLE 7 ⁶⁸ Ge- ⁶⁸ The leaching efficiency of the Ga generator;

TABLE 3 30mCi class or more in EXAMPLE 7 ⁶⁸ Ge- ⁶⁸ Of Ga generators ⁶⁸ Ge leakage rate;

TABLE 4 commercially available commonplace ⁶⁸ Ge- ⁶⁸ Ga generator performance.

TABLE 1

。

Analysis of results: as can be seen from Table 1, 2mCi was prepared from the adsorbents used in examples 1 to 5 ⁶⁸ Ge- ⁶⁸ The Ga-generator is arranged to generate a first voltage, ⁶⁸ the Ge leakage rate is less than or equal to 0.0001 percent, and accords with ⁶⁸ Ge- ⁶⁸ Basic performance and quality requirements of Ga generator, which can be used for ⁶⁸ Ge- ⁶⁸ Ga generators are commercially developed. It can be seen that, compared with the prior art ⁶⁸ Ge- ⁶⁸ Performance of Ga generator compared to 2mCi ⁶⁸ Ge- ⁶⁸ The initial leaching efficiency of the Ga generator is consistent with the prior art. This is due to ⁶⁸ Ge- ⁶⁸ Elution efficiency of Ga generator ⁶⁸ The Ge loading activity is in a range of 2-30mCi due to ⁶⁸ The Ge loading activity is smaller and is in an unsaturated state, so that the leaching efficiency is not different or is not obviously improved, but ⁶⁸ The Ge penetration rate is obviously reduced, which shows that the performance of the titanium dioxide prepared by the preparation method of the application is obviously improved compared with the prior art; on the other hand, the preparation method of comparative example 1 (replacement of inhibitor with ammonia water) or comparative example 2 (no secondary gel) cannot produce micron-sized titanium dioxide or has too low yield, and the adsorbents prepared in comparative example 3, comparative example 4, comparative example 5 are used for ⁶⁸ Ge- ⁶⁸ The Ga generator has too low performance, low leaching efficiency, and ⁶⁸ ge leakage is far above 0.001% and is difficult to use for commercial exploitation. Description of inhibitors in the preparation of titanium dioxide by sol-gel methodThe preparation method is characterized in that glacial acetic acid is needed to be definitely prepared, and the preparation method is needed to be roasted and washed in a secondary gel state, and specific roasting temperature and time are controlled, so that the titanium dioxide nano-particles with the particle size of 10-300 mu m, the titanium dioxide nano-particle size range of 10-100nm, the pore diameter of 5-30nm and the specific surface area of 30-100m can be prepared ² Titanium dioxide in anatase phase, which is improved as an adsorbent, and which has a smooth surface ⁶⁸ Ge- ⁶⁸ Performance of Ga generator.

Further, none of the titanium dioxide prepared in comparative examples 1-5 has commercial development prospects, whereas the titanium dioxide adsorbents prepared in examples 1-5 do not differ much in performance, so the subsequent test will be compared against the prior art for example 1.

TABLE 2

。

TABLE 3 Table 3

。

TABLE 4 Table 4

。

Analysis of results: as can be seen from tables 2 to 4, in the loading activity range of 30-85mCi, the initial leaching efficiency is 80% or more, up to 86%, and the leaching efficiency after long-term leaching (average leaching time of 6 months) can be maintained at 70% or more; several common to the prior market ⁶⁸ Ge- ⁶⁸ Ga generators are compared (Table 4), in ⁶⁸ On the premise of reducing the Ge leakage rate (about 0.0001%), the initial leaching efficiency is improved to more than 80%, and the leaching efficiency after 200 days of leaching can still be maintained to be more than 70%. This demonstrates the use of titanium dioxide prepared by the preparation method of the present application for ⁶⁸ Ge- ⁶⁸ The performance of the Ga generator is greatly improved.

Table 4 data long term rinse efficiency time specification: the prior art does not make clear regulations on long term leaching efficiencyThe rules of different manufacturers on long-term leaching are different, and the common published long-term leaching data are 200-day leaching time or 200-time leaching, and the medical grade ⁶⁸ Ge- ⁶⁸ The effective period of Ga generator is 12 months, chemical grade ⁶⁸ Ge- ⁶⁸ Ga generators are even up to 3 years (based on different performance criteria, e.g. Russian ⁶⁸ Ge- ⁶⁸ The leaching efficiency of the Ga generator is more than or equal to 45 percent, ⁶⁸ the Ge breakthrough was less than or equal to 0.005% and the shelf life was 3 years, so the application takes 200 days as the long term rinse efficiency versus time.

Further, FIG. 1 is a 50mCi scale ⁶⁸ Ge- ⁶⁸ The leaching efficiency change chart of the Ga generator for 200 days can show that the leaching efficiency slowly decreases along with the increase of leaching times and shows the trend of fluctuation up and down; based on the above trend, a variation formula (y= (-2.06×10) is obtained by linear fitting ^-4 ) x+0.798) and it can be found by calculation that after 12 months, the leaching efficiency can still be maintained above 70% (according to the formula, the leaching days x=365 are brought into the formula to calculate y=72%). And multiple times of leaching ⁶⁸ The Ge leakage penetration rate is stabilized at about 0.0001% and is far less than that of the European pharmacopoeia gallium chloride ⁶⁸ Ga]Solution standard pair ⁶⁸ The leakage rate of Ge is limited to be less than or equal to 0.001 percent.

Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.

Claims

1. The method comprises the following steps of ⁶⁸ Ge- ⁶⁸ Ga generator, characterized by comprising a packing cylinder for packing an adsorbent, the adsorbent being specifically adsorbed with ⁶⁸ Ge；

Wherein the adsorbent has a particle size of 10-300 μm,consists of 10-100nm nanometer particles with specific surface area of 30-100m ² And/g, the pore diameter is 5-30nm, the surface is smooth, and the granular titanium dioxide is in anatase phase.

2. According to claim 1 ⁶⁸ Ge- ⁶⁸ Ga generator, characterized in that the adsorbent particle size is 30-60 μm, 50-100 μm, 75-150 μm, 90-180 μm.

3. According to claim 1 or 2 ⁶⁸ Ge- ⁶⁸ The Ga generator is characterized in that the preparation method of the titanium dioxide adsorbent is a sol-gel method, and comprises the following steps:

4. A method according to claim 3 ⁶⁸ Ge- ⁶⁸ The Ga generator is characterized in that the adding amount of the titanium source solution and the purified water is 1: (0.5-10) in volume ratio, wherein the stirring speed of the dropwise adding mode is 10-100 revolutions/min while stirring, and the dripping speed is 1-100mL/min.

5. A method according to claim 3 ⁶⁸ Ge- ⁶⁸ The Ga generator is characterized in that the heating and heat preserving temperature is 110-180 ℃ and the time is 6-36h.

6. A method according to claim 3 ⁶⁸ Ge- ⁶⁸ The Ga generator is characterized in that ultrasonic treatment is utilized to carry out surface modification on solid particles, and the ultrasonic power is 50-1000W, and the time is 0.5-12 h.

7. A method according to claim 3 ⁶⁸ Ge- ⁶⁸ The Ga generator is characterized in that the first roasting temperature is 300-700 ℃, and the second roasting temperature is 400-700 ℃; the first roasting time is 1-12h, and the second roasting time is 1-6h.

8. According to claim 1 ⁶⁸ Ge- ⁶⁸ The Ga generator is characterized in that the packing cylinder is made of plastic chromatographic columns, glass tubes, quartz tubes and the like.

9. According to claim 1 ⁶⁸ Ge- ⁶⁸ Ga generator, characterized in that ⁶⁸ Ge- ⁶⁸ The Ga generator also comprises an elution pipeline and a lead shielding body.

10. According to claim 1 ⁶⁸ Ge- ⁶⁸ Ga generator, characterized in that, according to the loading ⁶⁸ Different Ge activities, bringing the above ⁶⁸ Ge- ⁶⁸ Ga generators are classified into different classes.