A cartridge type synthesis apparatus and method for preparing a radionuclide-labeled pharmaceutical

Abstract

The application discloses a kind of preparation of radionuclide labeled drug sleeve type synthesis device and method, belong to radioactivity biological medicine technical field, including feed unit, centrifugal component, material end control valve assembly, product end control valve, product collector and waste liquid collector;Feed unit is used to store the raw material reagent or preparation radionuclide labeled drug stock solution transported to centrifugal component;Centrifugal component is used to prepare radionuclide labeled drug stock solution using transported raw material reagent and carries out centrifugation, or centrifugation is carried out to the radionuclide labeled drug stock solution transported;Product collector is used to collect radionuclide labeled drug after centrifugation;Waste liquid collector is used to collect supernatant;Centrifugal component is selectively communicated with feed unit by material end control valve assembly, and is selectively communicated with product collector or waste liquid collector by product end control valve.This application can realize the automatic preparation of radionuclide labeled microparticle or cell drug, satisfy production specification requirement.

Description

Technical Field

[0001] This invention belongs to the field of radioactive biomedicine technology, specifically relating to a cassette-type synthesis apparatus and method for preparing radionuclide-labeled drugs. Background Technology

[0002] Radioactive particulate matter can play an important role in disease treatment. For example, yttrium-90 (… 90 Yttrium-labeled resin microspheres (SIR-Spheres®, average microsphere diameter 20–60 μm) and glass microspheres (TheraSphere®, average microsphere diameter 20–30 μm) are clinically used for interventional radiotherapy of unresectable hepatocellular carcinoma or metastatic liver cancer. 90 Y] Microspheres are injected into the blood supply arteries of liver tumors via interventional surgery, where they can block the tumor's capillaries. 90 Y emits high-energy beta rays to kill cancer cells at close range, with almost no effect on normal tissues. Therefore, it has the effect of reducing tumor volume, downstaging, and transforming mid-to-late stage liver cancer.

[0003] Colloids containing therapeutic beta radionuclides, such as yttrium-90, samarium-153, rhenium-186, phosphorus-32, dysprosium-165, erbium-169, and holmium-166, can be used for radiation-induced synovectomy. This is a minimally invasive technique that uses radionuclides to treat synovial inflammation. After the radioactive colloid is injected into the joint cavity, the emitted high-energy beta rays can directly kill inflamed synovial cells, inhibit angiogenesis, and promote synovial fibrosis and atrophy, thereby eliminating diseased synovial tissue without damaging normal joint structures. It is mainly used to treat refractory synovitis such as rheumatoid arthritis and hemophilic arthritis. To prevent leakage of the colloid from the joint through lymphatic drainage, the appropriate particle size of the radioactive colloid is 2–10 micrometers.

[0004] Technetium-99m ( 99m Tc-labeled thermoplastic red blood cells can be used for spleen imaging, including detecting ectopic spleens and assessing spleen function. In addition, live cell therapy has developed rapidly in recent years. This therapy uses the body's own live cells or modified live cells to treat diseases, showing significant therapeutic effects on many intractable diseases such as cancer, severe infections, and autoimmune diseases. Numerous live cell-based clinical trials have been conducted internationally, and various live cell preparations have been approved for marketing. However, it is difficult to assess the pharmacokinetic parameters of therapeutic live cells in vivo using traditional drug analysis techniques. The radionuclide labeling and nuclear medicine imaging techniques developed in recent years provide an advanced non-invasive method for tracking the distribution and pharmacokinetic properties of live cell drugs in vivo. For example, radioactive metal nuclides, such as zirconium-89 (Zrconium-89), can be used to label live cell drugs. 89 The chelate formed by the reaction of Zr with 8-hydroxyquinoline (Oxine)89 Zr-Oxine can effectively label live cells under mild conditions, which can then be used for nuclear medicine imaging. Some radionuclide-labeled live cell preparations have already been used in human clinical trials.

[0005] In the history of radiopharmaceutical development, manual preparation once played a crucial role. However, manual preparation exposes operators to radiation, and product quality is easily affected by human factors. Automated synthesis technology can significantly reduce the ionizing radiation dose received by operators, facilitate standardized production processes, and improve production efficiency. Therefore, automated radiopharmaceutical production technology has seen significant development and widespread application in recent years. Currently, most automated radiopharmaceutical preparation devices use cassette-type synthesis units. The cassettes used in cassette-type synthesis units are disposable consumables, allowing for simple and quick replacement, avoiding cross-contamination during automated preparation, and ensuring the safety and quality requirements of automated radiopharmaceutical preparation.

[0006] Centrifugation is a crucial separation and purification technique in the preparation of radionuclide-labeled microparticles and cells. However, existing cassette-type radiopharmaceutical synthesis devices generally lack structural components with centrifugation capabilities for microparticle or cell purification. The preparation of microparticle-based radiopharmaceuticals and radiolabeled cell preparations still primarily relies on manual operation. This production model carries a significant risk of product contamination and struggles to meet Good Manufacturing Practices (GMP) requirements, severely impacting the research, development, and clinical application of radiopharmaceuticals and cell-based drugs. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a cassette-type synthesis apparatus and method for preparing radionuclide-labeled drugs. The cassette-type synthesis apparatus provided by this invention is equipped with a centrifugation component for separation and purification, enabling automated preparation of radionuclide-labeled particulate and cellular drugs, improving the safety of radiopharmaceutical preparation, and meeting Good Manufacturing Practice (GMP) requirements.

[0008] This invention provides the following technical solution: In a first aspect, a cassette-type synthesis apparatus for preparing radionuclide-labeled drugs is provided, comprising a feeding unit, a centrifugation assembly, a material-end control valve assembly, a product-end control valve, a product collector, and a waste liquid collector; The feeding unit is used to deliver raw material reagents or radionuclide-labeled drug stock solution to the centrifugation assembly; The centrifugation assembly is used to prepare radionuclide-labeled drug stock solution using the raw materials and reagents supplied by the feeding unit and to centrifuge the prepared radionuclide-labeled drug stock solution; or it is used to centrifuge the radionuclide-labeled drug stock solution supplied by the feeding unit. The product collector is used to collect the radionuclide-labeled drug obtained after centrifugation by the centrifugation assembly; The waste liquid collector is used to collect the supernatant produced after centrifugation by the centrifuge assembly; The centrifugal assembly is selectively connected to the feeding unit via a material-end control valve assembly, and is also selectively connected to the product collector or the waste liquid collector via a product-end control valve.

[0009] Furthermore, the feeding unit includes an injection assembly and a storage assembly mounted on a ferrule. The injection assembly is selectively connected to the centrifugation assembly or the storage assembly via the material-end control valve assembly, for quantitatively supplying raw material reagents to the centrifugation assembly or the storage assembly. The storage assembly is selectively connected to the injection assembly or the centrifugation assembly via the material-end control valve assembly, for supplying raw material reagents or radionuclide-labeled drug stock solution to the centrifugation assembly. The storage assembly is also connected to a gas path, which is used to supply gas for pressurizing and stirring or pressurizing and transferring the raw material reagents or radionuclide-labeled drug stock solution, and / or to supply gas via the storage assembly to the centrifugation assembly for pressurizing and transferring the supernatant or radionuclide-labeled drug suspension produced after centrifugation.

[0010] Furthermore, the feeding unit is also equipped with a heating control unit for heating raw materials, reagents, or reaction intermediates.

[0011] Furthermore, the centrifugal assembly includes a centrifugal separation section mounted on a sleeve. The centrifugal separation section includes a centrifugal tube, a centrifugal cap, a sealing plug, a first conduit, a second conduit, a third conduit, a fourth conduit, and a fifth conduit. The centrifugal tube includes a vertical section and an inclined section connected to each other. The centrifugal cap is fitted over the sealing plug and rotatably connected to it. The sealing plug is fixed to one end of the vertical section of the centrifugal tube. One end of the first conduit is connected to the material end control valve assembly, and the other end is inserted into the centrifugal cap. One end of the second conduit is inserted into the sealing plug, and the other end extends into the inclined section of the centrifugal tube. One end of the third conduit is connected to the product control valve, and the other end is inserted into the centrifugal cap. One end of the fourth conduit is inserted into the sealing plug and rotatably connected to the other end of the third conduit in a nested manner. The other end of the fourth conduit extends into the bottom of the inclined section of the centrifugal tube. One end of the fifth conduit is embedded in the centrifugal cap, and the other end is connected to the outside air.

[0012] Furthermore, the centrifugation assembly also includes a centrifugation control unit, which includes a fixing rod and a rotating disk. The fixing rod is sleeved on the centrifugation cover for fixing the centrifugation cover, and the rotating disk is connected to the centrifugation tube for driving the centrifugation tube to centrifuge the radionuclide-labeled drug stock solution.

[0013] Furthermore, the centrifuge cover includes a centrifuge cover body, a first annular protrusion and a second annular protrusion disposed on the centrifuge cover body, wherein the second annular protrusion is disposed around the first annular protrusion; The sealing plug includes a sealing plug body, a first annular groove and a second annular groove disposed on the sealing plug body; the second annular groove is disposed around the first annular groove; The first annular protrusion is nested within the first annular groove and is rotatably connected to the first annular groove. The second annular protrusion is nested within the second annular groove and is rotatably connected to the second annular groove, with a gap in the vertical direction.

[0014] Furthermore, the first annular protrusion is provided with a first through hole, the first annular groove is provided with a fourth through hole corresponding to the first through hole, the second annular protrusion is provided with a second through hole and a third through hole, and the second annular groove is provided with a fifth through hole and a sixth through hole. One end of the first conduit is connected to the material end control valve assembly, and the other end is embedded in the second through hole. One end of the second conduit is embedded in the fifth through hole, and the other end passes through the vertical part of the centrifuge tube and extends into the inclined part. One end of the third conduit is connected to the product end control valve, and the other end is embedded in the first through hole. One end of the fourth conduit is embedded in the fourth through hole, and the other end passes through the vertical part of the centrifuge tube and extends into the bottom of the inclined part. One end of the fifth conduit is embedded in the third through hole, and the other end is connected to the outside air.

[0015] Furthermore, the vertical height of the end of the second conduit that extends into the centrifuge tube is higher than the vertical height of the end of the fourth conduit that extends into the centrifuge tube.

[0016] In a second aspect, a method for preparing a radionuclide-labeled drug using the cassette-type synthesis apparatus for preparing a radionuclide-labeled drug as described in the first aspect is provided, wherein the radionuclide-labeled drug is a radionuclide-labeled microparticle, and the method includes: The raw materials and reagents are loaded into the feeding unit respectively. The raw materials and reagents are raw materials and reagents used to prepare radionuclide labeled microparticles, including radionuclide solution, microparticles to be labeled, pH buffer solution, washing solution and preparation medium. The material end control valve assembly is controlled to pressurize the liquid storage assembly by venting air, transfer and mix the raw materials and reagents, carry out the radionuclide labeling reaction, and start the heating control unit to heat and keep warm to obtain the radionuclide labeled microparticle drug stock solution. The material-side control valve assembly is controlled to add radionuclide-labeled microparticle drug stock solution to the centrifuge tube of the centrifuge assembly; the rotating disk of the centrifuge assembly is controlled to centrifuge the centrifuge tube; after centrifugation, the product-side control valve is controlled to pressurize the centrifuge tube by introducing gas, and the supernatant in the centrifuge tube is transferred to the waste liquid collector; a cleaning solution is injected into the centrifuge tube and mixed evenly, centrifuged and the supernatant is removed, and then a formulation medium is injected to obtain a suspension of radionuclide-labeled microparticles; Control the product-side control valve to transfer the suspension of radionuclide-labeled microparticles to the product collector for storage.

[0017] Furthermore, the particle size in the radionuclide-labeled microparticle suspension is 0.2~100 μm.

[0018] Thirdly, a method for preparing a radionuclide-labeled drug using the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs as described in the first aspect is provided, wherein the radionuclide-labeled drug is radionuclide-labeled cells, and the method includes: The raw materials and reagents are loaded into the feeding unit respectively. The raw materials and reagents are raw materials and reagents used to prepare radionuclide-labeled cells, including cell suspension, radionuclide solution, washing solution and preparation medium. Control the material end control valve assembly to add cell suspension to the centrifuge tube of the centrifuge assembly; control the rotating disk of the centrifuge assembly to centrifuge the centrifuge tube; after centrifugation, control the product end control valve to pressurize the centrifuge tube by introducing gas, and transfer the supernatant to the waste liquid collector. The material end control valve assembly is used to add a radionuclide solution to a centrifuge tube for reaction. After adding a washing solution and mixing evenly, the mixture is centrifuged multiple times and the supernatant is removed. Then, a formulation medium is added and mixed evenly to obtain a radionuclide-labeled cell suspension. Control the product-side control valve to pressurize the centrifuge tube by introducing gas, and transfer the radionuclide-labeled cell suspension to the product collector for storage.

[0019] Compared with the prior art, the beneficial effects of the present invention are: The cassette-type synthesis apparatus provided by this invention can be used for the automated preparation of radionuclide-labeled drugs, such as radiotherapy radionuclide-labeled microparticle drugs and radioimaging radionuclide-labeled cell preparations, achieving high radiolabeling efficiency. The cassette-type synthesis apparatus provided by this invention is equipped with a centrifugation component, which can realize the separation and purification of radionuclide-labeled drugs during the labeling process, with minimal damage to living cells during the labeling and purification process. It can significantly reduce the contamination risk of traditional manual processes, achieve standardization of production processes, ensure product quality, and promote the clinical research and medical application of these radiopharmaceuticals. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs in Embodiment 2 of the present invention; Figure 2 This is a schematic diagram of the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs with the addition of a third storage bottle in Embodiment 2 of the present invention; Figure 3 This is a schematic diagram of the centrifuge assembly in Embodiment 2 of the present invention; Figure 4 This is a schematic diagram of the centrifuge cap in Embodiment 2 of the present invention; Figure 5 This is a schematic diagram of the sealing plug in Embodiment 2 of the present invention; Figure 6 This is a cross-sectional structural diagram of the sealing plug in Embodiment 2 of the present invention.

[0021] The diagram is labeled as follows: 1. Injection assembly; 11. First syringe; 12. Second syringe; 2. Liquid storage assembly; 21. First liquid storage bottle; 22. Second liquid storage bottle; 23. Third liquid storage bottle; 3. Centrifugation assembly; 31. Centrifugation control unit; 311. Fixing rod; 312. Rotating disc; 32. Centrifugation separation unit; 321. Centrifuge tube; 322. Centrifuge cap; 3221. First annular protrusion; 3222. Second annular protrusion; 3223. Centrifuge cap body; 3224. First through hole; 3225. Second through hole; 3226. Third through hole; 323. Sealing plug; 3231. First annular groove; 3232. Second annular groove; 3233. Sealing plug. 3234, fourth through hole; 3235, fifth through hole; 3236, sixth through hole; 324, first conduit; 325, second conduit; 326, third conduit; 327, fourth conduit; 328, fifth conduit; 4, material end control valve assembly; 41, first control valve; 42, first second control valve; 43, first third control valve; 44, first fourth control valve; 45, first gas control valve; 46, second gas control valve; 47, third gas control valve; 48, fourth gas control valve; 5, product end control valve; 6, product collector; 7, waste liquid collector; 8, second control valve; 9, feeding unit; 10, heating control unit. Detailed Implementation

[0022] The present invention will be further described below with reference to the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and should not be used to limit the scope of protection of the present invention.

[0023] It should be noted that in the description of this invention, the terms "front", "rear", "left", "right", "upper", "lower", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and do not require that this invention must be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting this invention.

[0024] In the description of this invention, it should be understood that the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined with "first," "second," etc., may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more. The terms "comprising," "including," "having," "containing," etc., as used herein, are open-ended terms, meaning that they include but are not limited to.

[0025] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0026] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0027] Example 1

[0028] This embodiment provides a cassette-type synthesis apparatus for preparing radionuclide-labeled drugs, including a feeding unit 9, a centrifugation assembly 3, a material-end control valve assembly 4, a product-end control valve 5, a product collector 6, and a waste liquid collector 7.

[0029] The feeding unit 9 is used to deliver raw material reagents or radionuclide-labeled drug stock solutions to the centrifugation assembly 3; The centrifugation assembly 3 is used to prepare radionuclide-labeled drug stock solution using the raw materials and reagents supplied by the feeding unit 9 and to centrifuge the prepared radionuclide-labeled drug stock solution; or it is used to centrifuge the radionuclide-labeled drug stock solution supplied by the feeding unit 9. The product collector 6 is used to collect the radionuclide-labeled drug obtained after centrifugation by the centrifugation assembly 3; The waste liquid collector 7 is used to collect the supernatant produced after centrifugation by the centrifugal assembly 3; The centrifugal assembly 3 is selectively connected to the feeding unit 9 via the material end control valve assembly 4, and is also selectively connected to the product collector 6 or the waste liquid collector 7 via the product end control valve 5.

[0030] In this embodiment, the present invention provides a cassette-type synthesis apparatus for preparing radionuclide-labeled drugs. The structural components of the cassette-type synthesis apparatus are integrated into one unit in a cassette manner, enabling automated preparation of radionuclide-labeled drugs. By activating the material-end control valve assembly 4, the raw material reagents or radionuclide-labeled drug stock solution in the feeding unit 9 are transferred to the centrifugation assembly 3. In this embodiment, the raw material reagents can be directly fed into the centrifugation assembly 3 by the feeding unit 9, and then mixed evenly in the centrifugation assembly 3 to obtain the radionuclide-labeled drug stock solution. Then, the centrifugation assembly 3 is activated for centrifugation to obtain the radionuclide-labeled drug and supernatant. Alternatively, the radionuclide-labeled drug stock solution can be directly fed into the centrifugation assembly 3 by the feeding unit 9, followed by centrifugation to obtain the radionuclide-labeled drug and supernatant. By selectively activating the product-side control valve 5, when the centrifuge assembly 3 and waste liquid collector 7 are connected, the supernatant obtained after centrifugation in the centrifuge assembly 3 is transferred to the waste liquid collector 7 by gas pressurization; when the centrifuge assembly 3 and product collector 6 are connected, the radionuclide-labeled drug obtained after centrifugation in the centrifuge assembly 3 is transferred to the product collector 6 for storage by gas pressurization. Through the coordinated operation of various components and control valves, this invention can achieve separation and purification during the radionuclide-labeled drug labeling process, significantly improving the efficiency of separation and purification, reducing the pollution risk of traditional manual operation processes, ensuring product quality, and meeting the standardized requirements of production.

[0031] Example 2

[0032] Based on the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs provided in Example 1, this embodiment provides a cassette-type synthesis apparatus for preparing radionuclide-labeled drugs, including a feeding unit 9, a centrifugation assembly 3, a material end control valve assembly 4, a product end control valve 5, a product collector 6, and a waste liquid collector 7. Each component is connected by a fluid transmission pipeline according to the fluid transfer flow path required by the synthesis process of radionuclide-labeled particulate drugs or radionuclide-labeled cell drugs, and the cassette achieves integrated design.

[0033] like Figure 1As shown, the feeding unit 9 includes an injection assembly 1 and a liquid storage assembly 2 mounted on a ferrule. The injection assembly 1 includes multiple syringes connected in sequence. In this embodiment, the injection assembly 1 includes a first syringe 11 and a second syringe 12 connected in sequence, which are used to quantitatively deliver raw materials and reagents to the centrifugation assembly 3 or the liquid storage assembly 2, respectively. In some possible embodiments, a syringe holder can be provided to fix the syringes, and an automatic mechanical handle can be used to push and pull the syringe piston rod. In this embodiment, the ferrule-type synthesis device provided by the present invention is provided with an injection assembly control unit, which is used to control the pushing and pulling of each syringe to quantitatively transfer liquid to the liquid storage assembly 2 or the centrifugation separation section 32. The liquid storage assembly 2 includes a first liquid storage bottle 21 and a second liquid storage bottle 22. The material end control valve assembly 4 includes a first control valve 41, a first second control valve 42, a first third control valve 43, a first fourth control valve 44, a first gas control valve 45, a second gas control valve 46, and a third gas control valve 47. The first syringe 11 is selectively connected to the first second control valve 42 through the first first control valve 41, and the first second control valve 42 is also selectively connected to the second syringe 12 and the first third control valve 43. The first third control valve 43 is also selectively connected to the first liquid storage bottle 21 and the first fourth control valve 44. The first fourth control valve 44 is also selectively connected to the second liquid storage bottle 22 and the centrifugal separation unit 32. The first liquid storage bottle 21 and the second liquid storage bottle 22 are also connected to the gas path. In this embodiment, the first liquid storage bottle 21 is connected to the gas path through an air pipeline and the first gas control valve 45, and the second liquid storage bottle 22 is connected to the gas path through an air pipeline and the second gas control valve 46. In one possible embodiment, the first gas control valve 45 and the second gas control valve 46 are two-way valves. The introduced gas can agitate the liquid in the liquid storage bottle. It can also control the on / off time of the valve to apply gas pressure to the liquid storage assembly 2, so that the liquid in the liquid storage bottle can be transferred to other liquid storage bottles or the centrifugal assembly 3. It can also control the on / off time of the valve to transport gas through the liquid storage assembly 2 to the centrifugal assembly 3, so as to pressurize and agitate the solution in the centrifugal assembly 3 or pressurize and transfer the solution in the centrifugal assembly 3 to the outside. In this embodiment, the ferrule-type synthesis device provided by the present invention is further provided with a valve control unit to control the opening and closing of each valve to realize the flow of fluid or gas in the pipeline.

[0034] The feeding unit 9 is also equipped with a heating control unit 10. For example... Figure 2 As shown, the liquid storage assembly 2 has a heating control unit 10 on its liquid storage bottle, which heats the liquid storage bottle using hot air or a heating plate at a set temperature. In one possible embodiment, the heating control unit 10 is a hot air fan with temperature control function.

[0035] In some possible embodiments, the raw material reagents in the injection assembly 1 and the reservoir assembly 2 include one or more of the following: radionuclide solution, microsphere suspension, cell suspension, pH buffer, washing solution, or formulation medium.

[0036] In some possible embodiments, depending on reagent requirements, a syringe for injection assembly 1 or a reservoir bottle for reservoir assembly 2 can be added, along with a control valve to control the flow of liquid or the gas path. For example... Figure 2 As shown, in one possible embodiment, a third storage bottle 23 can also be added between the centrifuge assembly 3 and the product-side control valve 5. The material-side control valve assembly 4 is further equipped with a second control valve 8 and a fourth gas control valve 48. The third storage bottle 23 is used to hold raw material reagents and is selectively connected to other components through the second control valve 8. At the same time, the valve port of the product-side control valve 5 is adjusted according to the drainage requirements. The third storage bottle 23 is connected to a gas circuit through the fourth gas control valve 48. Gas is introduced into the third storage bottle 23 through the gas circuit to pressurize and stir the liquid in the bottle or to pressurize and transfer the liquid in the bottle out.

[0037] like Figure 1 and Figure 3As shown, the centrifuge assembly 3 includes a centrifuge control unit 31 and a centrifuge separation unit 32. The centrifuge separation unit 32 is mounted on a sleeve and includes a centrifuge tube 321, a centrifuge cover 322, a sealing plug 323, a first conduit 324, a second conduit 325, a third conduit 326, a fourth conduit 327, and a fifth conduit 328. The centrifuge tube 321 includes a vertical portion and an inclined portion that are connected to each other. The centrifuge cover 322 is fitted over the sealing plug 323, and the sealing plug 323 is fixed to one end of the vertical portion of the centrifuge tube 321. The centrifuge cover 322 tightly wraps around the outer edge of the sealing plug 323, but there is no fixed connection point between the centrifuge cover 322 and the sealing plug 323. The centrifuge cover 322 is rotatably connected to the sealing plug 323. When the centrifuge tube 321 and the sealing plug 323 rotate simultaneously, the centrifuge cover 322 can remain stationary. One end of the first conduit 324 is connected to the first control valve 44 of the material end control valve assembly 4, and the other end extends into the centrifuge cover 322. One end of the second conduit 325 extends into the sealing plug 323, and the other end extends into the inclined portion of the centrifuge tube 321. One end of the third conduit 326 is selectively connected to the product collector 6 or the waste liquid collector 7 via the product end control valve 5, and the other end extends into the centrifuge cap 322. One end of the fourth conduit 327 extends into the sealing plug 323, and the other end extends into the bottom of the inclined portion of the centrifuge tube 321. The end of the third conduit 326 extending into the centrifuge cap 322 is rotatably connected to the end of the fourth conduit 327 extending into the sealing plug 323. In one possible embodiment, the third conduit 326 and the fourth conduit 327 are nested together and can rotate freely relative to each other. One end of the fifth conduit 328 is embedded in the centrifuge cap 322, and the other end is connected to outside air via the third gas control valve 47 to balance the air pressure inside the centrifuge tube 321. In one possible embodiment, the third gas control valve 47 is a two-way valve. In one possible embodiment, the third gas control valve 47 is a three-way valve, and the fifth conduit 328 can selectively connect to the gas path, directly supplying gas to the centrifuge tube 321 for pressurizing and stirring or pressurizing and transferring the liquid inside the tube. By pressurizing the gas and selectively opening the product-end control valve 5, the radionuclide-labeled drug in the centrifuge assembly 3 of the centrifuge tube 321 can be transferred to the product collector 6, and the supernatant can be transferred to the waste liquid collector 7. In addition, by introducing gas into the centrifuge tube 321, the liquid inside the tube can also be pressurized and stirred, so that the substances can be mixed evenly.

[0038] like Figures 1-3As shown, the centrifugation control unit 31 can drive the centrifugation separation unit 32 to rotate, thereby centrifuging the radionuclide-labeled drug stock solution within the centrifugation assembly 3. The centrifugation control unit 31 includes a fixing rod 311 and a rotating disk 312. In some possible embodiments, the positions of the fixing rod 311 and the rotating disk 312 in the centrifugation control unit 31 can be arbitrarily adjusted according to the size of the centrifugation separation unit 32. The fixing rod 311 is sleeved on the outside of the centrifugation cover 322 to fix the centrifugation cover 322. The rotating disk 312 is connected to the centrifugation tube 321 and is used to drive the centrifugation tube 321 to rotate to achieve centrifugation. In one possible embodiment, a support can be provided on the rotating disk 312, and the centrifugation tube 321 is mounted on the support. When the rotating disk 312 rotates, the centrifugation cover 322 remains stationary. The rotating disk 312 drives the centrifugation tube 321 and the sealing plug 323 to rotate around the vertical line of the center of the upper half of the centrifugation tube 321, so that the particulate matter or cells in the radionuclide-labeled drug stock solution gather at the bottom end of the inclined part of the centrifugation tube 321. In some possible embodiments, the driving force of the centrifugation control unit 31 is provided by the centrifugation control unit, which sets the automated process parameters according to actual operational needs, and automatically centrifuges the radionuclide-labeled drug stock solution to obtain the radionuclide-labeled drug.

[0039] like Figure 4 As shown, the centrifuge cover 322 includes a centrifuge cover body 3223, a first annular protrusion 3221 and a second annular protrusion 3222 disposed on the centrifuge cover body 3223, the second annular protrusion 3222 surrounding the first annular protrusion 3221. In one possible embodiment, the first annular protrusion 3221 is located at the center of the centrifuge cover body 3223 near the sealing plug 323, and the second annular protrusion 3222 is located on the centrifuge cover body 3223 near the sealing plug 323, with the first annular protrusion 3221 as the center. Figure 5 As shown, the sealing plug 323 includes a sealing plug body 3233, a first annular groove 3231 and a second annular groove 3232 disposed on the sealing plug body 3233, the second annular groove 3232 surrounding the first annular groove 3231. In one possible embodiment, the first annular groove 3231 is located at the center of the sealing plug body 3233 near the centrifuge cap 322, and the second annular groove 3232 is located on the side of the sealing plug body 3233 near the centrifuge cap 322, with the first annular groove 3231 as the center. The first annular protrusion 3221 is tightly nested and connected to the first annular groove 3231, and the second annular protrusion 3222 is tightly nested and connected to the second annular groove 3232, with a gap in the vertical direction, allowing the corresponding protrusion and groove to rotate relative to each other.

[0040] like Figures 3-6As shown, the first annular protrusion 3221 has a first through hole 3224 at its center, and the first annular groove 3231 has a fourth through hole 3234 corresponding to the first through hole 3224. The second annular protrusion 3222 has a second through hole 3225 and a third through hole 3226, and the second annular groove 3232 has a fifth through hole 3235 and a sixth through hole 3236.

[0041] like Figures 1-6 As shown, one end of the first conduit 324 is connected to the material-end control valve assembly 4, and the other end is embedded in the second through hole 3225. One end of the second conduit 325 is embedded in the fifth through hole 3235, and the other end passes through the vertical part of the centrifuge tube 321 and extends into the inclined part. One end of the third conduit 326 is connected to the product-end control valve 5, and the other end is embedded in the first through hole 3224. One end of the fourth conduit 327 is embedded in the fourth through hole 3234, and the other end passes through the vertical part of the centrifuge tube 321 and extends into the bottom of the inclined part. The first through hole 3224 and the fourth through hole 3234 correspond to each other, and the third conduit 326 and the fourth conduit 327 are nested and rotated together to form a liquid communication passage. One end of the fifth conduit 328 is embedded in the third through hole 3226, and the other end is connected to the outside air. There is a gap between the second annular protrusion 3222 and the second annular groove 3232. When the control valve assembly 4 and the gas path are selectively activated, the raw material reagent or radionuclide-labeled drug stock solution in the feeding unit 9 will flow into the second annular groove 3232 through the first conduit 324, and then into the centrifuge tube 321 through the second conduit 325 or the sixth through hole 3236. In addition, when the fifth conduit 328 is selectively closed, the liquid storage assembly 2 can also provide gas to the centrifuge tube 321 through the first conduit 324 via the second conduit 325 or the sixth through hole 3236 to pressurize and stir the liquid in the centrifuge tube 321, or to provide gas to pressurize and transfer the supernatant or radionuclide-labeled drug after centrifugation, thereby realizing the transfer of liquid in the centrifuge tube 321 to the outside.

[0042] In this embodiment, the shapes of the second conduit 325 and the fourth conduit 327 are designed according to the inclined portion of the centrifuge tube 321, and the vertical height of the other end of the second conduit 325 is higher than that of the other end of the fourth conduit 327. The raw material reagent or the radionuclide-labeled drug stock solution to be centrifuged can be injected into the centrifuge tube 321 by activating the material-end control valve assembly 4 and opening the gas path; the product-end control valve 5 can be selectively activated by opening the gas path to discharge the radionuclide-labeled drug suspension obtained after centrifugation in the centrifuge tube 321 into the product collector 6 or to discharge the supernatant generated after centrifugation in the centrifuge tube 321 into the waste liquid collector 7. When the centrifugal separation section 32 performs centrifugation, the first conduit 324 and the third conduit 326 are nested in the through hole of the centrifugal cover 322, so they remain stationary with the centrifugal cover 322. The second conduit 325 and the fourth conduit 327 are embedded in the through hole of the sealing plug 323. The second conduit 325 will rotate with the sealing plug 323, and the fourth conduit 327 will rotate around its own central axis, ultimately ensuring the rotation of the centrifugal tube 321 and the sealing plug 323 relative to the centrifugal cover 322.

[0043] In some possible embodiments, the container for holding the solution is made of glass or plastic, the control valves of the product-side control valve 5 and the material-side control valve assembly 4 are made of engineering plastic, the fluid transmission pipeline is made of engineering plastic, the centrifugal separation section 32 is made of engineering plastic, and the injection assembly 1 and the liquid storage assembly 2 can also be connected to a sterile needle filter.

[0044] In some possible embodiments, the ferrule-type synthesis apparatus provided by the present invention uses PLC programs, PC programs or other automatic control methods to control the operation of various units and components, including controlling the valves in the fluid pipeline (such as the material end control valve assembly 4 and the product end control valve 5) to connect or disconnect according to a set time, controlling the push and pull of the injection assembly 1, the opening and closing of the gas pipeline, the start and stop of the centrifugation assembly 3, and the operation of other steps in the radionuclide labeling process. By setting the automated process parameters of the control end, the automated operation of each functional module can be realized.

[0045] Example 3

[0046] Based on the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs in Example 1 or Example 2, this embodiment provides a method for preparing radionuclide-labeled drugs. In this embodiment, the radionuclide-labeled drug is a radiolabeled microparticle, and the method includes the following steps.

[0047] S1. Load the raw materials and reagents into the feeding unit 9. The raw materials and reagents are the raw materials and reagents used to prepare radionuclide labeled microparticles, including radionuclide solution, microparticles to be labeled, pH buffer solution, cleaning solution and preparation medium.

[0048] S2. Control the material end control valve assembly 4, introduce gas into the liquid storage assembly 2 to pressurize it, transfer and mix the raw material reagents, carry out the radionuclide labeling reaction, and start the heating control unit 10 to heat and keep it warm to obtain the radionuclide labeled microparticle drug stock solution.

[0049] S3. Control the material end control valve assembly 4 to add the radionuclide-labeled microparticle drug stock solution to the centrifuge tube 321 of the centrifuge assembly 3; control the rotating disk 312 of the centrifuge assembly to centrifuge the centrifuge tube 321; after centrifugation, control the product end control valve 5 to pressurize the centrifuge tube 321 by introducing air through the first conduit 324, and transfer the supernatant in the centrifuge tube 321 to the waste liquid collector 7; inject cleaning solution into the centrifuge tube 321 to mix evenly, centrifuge and remove the supernatant, and inject cleaning solution again to obtain a radionuclide-labeled microparticle suspension.

[0050] S4. Control the product end control valve 5 to transfer the suspension of radionuclide-labeled microparticles to the product collector 6 for storage.

[0051] In some possible embodiments, a particle generation reaction is performed before the radionuclide labeling reaction.

[0052] 1. Load the raw materials and reagents into the feeding unit 9 respectively. The raw materials and reagents include radioactive nuclide solution, reaction solution for preparing microparticles, pH buffer solution, cleaning solution and preparation medium.

[0053] 2. Control the material end control valve assembly 4, introduce gas into the liquid storage assembly 2 to pressurize it, transfer and mix the raw material reagents, carry out the microparticle generation reaction, and start the heating control unit 10 to heat and keep it warm to obtain microparticles.

[0054] In some possible embodiments, after connecting the ferrule and the container or syringe containing the required chemical reagents and radionuclides, as well as the fluid lines, automated preparation and purification can be performed according to a programmed sequence to obtain radionuclide-labeled particulate drug formulations, such as those for liver cancer or liver metastases. 90 Y-labeled microspheres and radionuclide-labeled microparticles for radiotherapy synovectomy. These microparticle drugs have a particle size in the micrometer range, or as low as hundreds of nanometers, preferably in the range of 0.2 to 100 micrometers.

[0055] The radiochemical labeling rate of the product can be obtained by comparing the radioactivity of the prepared radiolabeled microparticle product with the activity of the radionuclide used to label the microparticle drug.

[0056] The radiochemical labeling rate of radiolabeled microparticle products = radioactivity of radiolabeled microparticle products / radioactivity of the nuclide added during labeling (corrected to the same measurement time point) × 100%.

[0057] Take a portion of the prepared radioactive particulate product suspension and transfer it to a gamma counter tube. Centrifuge to precipitate the particulate drug. Transfer the supernatant completely to another gamma counter tube. Measure the radioactivity of the supernatant and the precipitate collected after centrifugation, respectively. The radiochemical purity of the product can then be calculated.

[0058] Radiochemical purity of radiolabeled microparticle products = Radioactivity of the precipitate collected after centrifugation / Radioactivity of the sample before centrifugation (corrected to the same measurement time point) × 100%.

[0059] Example 4

[0060] Based on the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs provided in Example 1 or Example 2, this embodiment provides a method for preparing radionuclide-labeled drugs. In this embodiment, the radionuclide-labeled drug is radiolabeled cells, and the method includes the following steps.

[0061] S1. Load the raw materials and reagents into the feeding unit 9. The raw materials and reagents are the raw materials and reagents used to prepare radionuclide-labeled cells, including cell suspension, radionuclide solution, washing solution and preparation medium.

[0062] S2. Control the material end control valve assembly 4 to add cell suspension to the centrifuge tube 321 of the centrifuge assembly 3; control the rotating disk 312 of the centrifuge assembly 3 to centrifuge the centrifuge tube 321; after centrifugation, control the product end control valve 5 to pressurize the centrifuge tube 321 through the first conduit 324, and transfer the supernatant in the centrifuge tube 321 to the waste liquid collector 7.

[0063] S3. Control the material end control valve assembly 4, add radionuclide solution to centrifuge tube 321 to react, add washing liquid and mix evenly, centrifuge multiple times and remove supernatant, add preparation medium and mix evenly to obtain radionuclide labeled cell suspension.

[0064] S4. Control the product end control valve 5 to introduce gas into the centrifuge tube 321 to pressurize it, and transfer the radionuclide-labeled cell suspension to the product collector 6 for storage.

[0065] In some possible embodiments, the radionuclide solution is a radionuclide solution, such as... 64 Cu、 111 In、 89 A radioactive chelate solution (M-Oxine) is formed by mixing a Zr solution with Oxine.

[0066] Radioactive cell-based drug formulations are radionuclide-labeled cell preparations used for nuclear medicine imaging or pharmacokinetic studies, such as those used for spleen imaging. 99m Tc-labeled heat-denatured erythrocytes, 89 Zr-labeled therapeutic live cells used to trace in vivo distribution and pharmacokinetics studies include stem cells, bone marrow cells, erythrocytes, leukocytes, macrophages, CAR-T cells, CAR-NK cells, or CLT cells.

[0067] The radiochemical labeling efficiency can be obtained by comparing the radioactivity of the prepared radiolabeled cell product with the activity of the radionuclide used to label the cells.

[0068] Radiochemical labeling rate of radiolabeled cell products = Radioactivity of radiolabeled cell products / Radioactivity of the nuclide added during labeling (corrected to the same measurement time point) × 100%.

[0069] Take a portion of the prepared radiolabeled cell product suspension and transfer it to a gamma counter tube. Centrifuge to precipitate the cells, and completely transfer the supernatant to another gamma counter tube. Measure the radioactivity of the supernatant and the cell precipitate collected after centrifugation, respectively, to calculate the radiochemical purity of the radiolabeled cell product.

[0070] Radiochemical purity of radiolabeled cell products = Radioactivity of cell pellet collected after centrifugation / Radioactivity of cell sample before centrifugation (corrected to the same measurement time point) × 100%.

[0071] Example 5

[0072] Based on the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs provided in Example 1 or Example 2, and the method for preparing radionuclide-labeled drugs provided in Example 3, this example prepares... 177 Lu-labeled hydroxyapatite microparticles.

[0073] Pre-load 10 mg of hydroxyapatite (HA) microspheres with a particle size range of 1-10 micrometers and 5 ml of sterile water into the first storage bottle 21, and pre-load 0.1-0.3 ml of 15 mCi [ into the second storage bottle 22]. 177 LuCl3 / 0.1 mol / L HCl aqueous solution. Pre-fill the first syringe 11 with 2 ml of aqueous solution containing 15 mg sodium bicarbonate, and pre-fill the second syringe 12 with 20 ml of sterile physiological saline. Connect the injection assembly 1 and the reservoir assembly 2 to the ferrule. The fifth conduit 328 of the centrifuge assembly 3 is connected to a gas filter; when this valve is open, it maintains pressure balance inside and outside the centrifuge tube 321. Set the automated process parameters of the synthesis apparatus and perform the following preparations.177 The steps for labeling HA microspheres with Lu.

[0074] 1. The control unit of the injection assembly transfers 2 ml of sodium bicarbonate aqueous solution from the first syringe 11 to the first storage bottle 21.

[0075] 2. Open the clean air passage connected to the first storage bottle 21, inject clean air into the first storage bottle 21, and transfer the suspension containing HA in the reagent bottle to the bottle containing […]. 177 The second storage bottle 22 of Lu]LuCl3.

[0076] 3. Activate the heating control unit 10 to heat the liquid in the second storage bottle 22 to 40°C and maintain this temperature for 30 minutes. Introduce clean air into the second storage bottle 22, along with the aqueous solution... 177 Lu-labeled HA microspheres were transferred into centrifuge tube 321 via an appropriate fluid pathway.

[0077] 4. Start the centrifugation control unit 31 and centrifuge the centrifuge tube 321 at 5000 rpm for 5 minutes. After stopping the centrifugation, introduce clean air and transfer most of the supernatant from the centrifuge tube 321 to the waste liquid collector 7.

[0078] 5. Control the injection assembly control unit to inject 5 ml of sterile saline from the second syringe 12 into the centrifuge tube 321.

[0079] 6. Repeat steps 4 and 5.

[0080] 7. Repeat step 4, then control the injection assembly control unit to inject 10 ml of sterile saline from the second syringe 12 into the centrifuge tube 321. Then pressurize the centrifuge tube 321 by introducing clean air. 177 The Lu-labeled HA microsphere suspension was transferred from centrifuge tube 321 to product collector 6.

[0081] according to 177 The activity of Lu-labeled HA microspheres and the labeling agent used [ 177 The activity of Lu]LuCl3 was used to calculate the radiochemical yield of the radiolabeled microparticle product, which was greater than 96%; 177 Lu-labeled HA microsphere suspension was prepared by centrifugation to separate the microspheres from the aqueous phase. The activity was measured and calculated. 177 The radiochemical purity of the Lu-labeled HA microspheres is greater than 99%.

[0082] Example 6

[0083] Based on the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs provided in Example 1 or Example 2, and the method for preparing radionuclide-labeled drugs provided in Example 4, this example prepares...89 Zr-labeled human umbilical cord mesenchymal stem cells.

[0084] 1. Take 0.8 mCi [ 89 The Zr-oxalic acid source solution was adjusted to pH 7 by adding 9 volumes of 0.1 mol / L HEPES, pH 7.2 buffer solution and approximately 0.65 volumes of 1 mol / L Na₂CO₃ solution. Then, the solution was processed according to a 1 mCi ratio. 89 Zr: 25 μg Oxine was added to a 5 mg / ml Oxine solution dissolved in DMSO and mixed well. After reacting at room temperature for 15 minutes, PBS buffer was added to dilute to 3 ml to obtain […]. 89 Zr]Zr-oxine solution. [ 89 Zr]Zr-oxine solution was drawn into the first syringe 11, and 20 ml of PBS buffer was pre-filled into the second syringe 12. The 20 ml solution containing 1.0 × 10⁻⁶ PBS was then added. 8 A suspension of personal umbilical cord mesenchymal stem cells is placed into the first reservoir bottle 21, and 25 ml of the preparation medium for preserving human umbilical cord mesenchymal stem cells is placed into the second reservoir bottle 22. The injection assembly 1, reservoir assembly 2, sterile needle filter, and fluid lines are connected on the ferrule according to the fluid transfer path required by the synthetic process of radiolabeled cell drugs.

[0085] 2. Open the gas path connected to the first storage bottle 21 and the gas path connected to the fifth conduit 328 to balance the air pressure inside and outside the centrifuge tube 321. Transfer the cell suspension in the first storage bottle 21 to the centrifuge tube 321 by pressurizing the air.

[0086] 3. Start the centrifugation control unit 31 and centrifuge the centrifuge tube 321 at a preset speed for a period of time, so that the cells aggregate at the bottom of the tube. In some possible embodiments, the speed is 1200~2000 rpm and the centrifugation time is 10 minutes.

[0087] 4. Then close the air passage of the fifth conduit 328, and pressurize the centrifuge tube 321 by introducing clean air through the first conduit 324, so that most of the supernatant is transferred from the centrifuge tube 321 to the waste liquid collector 7 along the fourth conduit 327 and the third conduit 326.

[0088] 5. Activate the syringe control unit and dispense 3 ml of the first syringe 11. 89 The Zr-oxine solution was transferred into centrifuge tube 321 through the first conduit 324.

[0089] 6. To be [ 89After Zr-oxine reacts with cells in centrifuge tube 321 for 20 minutes, the syringe control unit is activated to transfer 5 ml of PBS solution from the second syringe 12 into centrifuge tube 321.

[0090] 7. Repeat steps 3 and 4.

[0091] 8. Control the syringe control unit to transfer 15 ml of PBS from the second syringe 12 to the centrifuge tube 321, and repeat steps 3 and 4 again.

[0092] 9. Open the gas path of the second storage bottle 22, adjust the orientation of each three-way valve, and transfer the preparation medium from the second storage bottle 22 to the centrifuge tube 321 through the first conduit 324 by pressurizing the air.

[0093] 10. Close the gas path of the fifth conduit 328, and pressurize the centrifuge tube 321 by injecting air through the first conduit 324, marking the centrifuge tube 321. 89 The Zr cell suspension was transferred to product collector 6 to obtain 89 Zr-labeled human mesenchymal stem cell preparation.

[0094] In some possible embodiments, the measured 89 The radioactivity of Zr-labeled cell preparations, calculated as a radiochemical labeling rate, is generally in the range of 50-60%. 0.1 ml of the radiolabeled cell suspension is taken, centrifuged, and the radioactivity of the separated precipitate cells is measured. The calculated radioactivity is then used to determine the labeling rate. 89 The radiochemical purity of Zr-labeled cells is generally in the range of 90% to 92%. After mixing 15 ml of cell suspension with 15 ml of 0.2% trypan blue staining solution, the cell viability is detected using an automated cell counter. The measured cell viability is usually not significantly different from that of cells before labeling.

[0095] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A cassette-type synthesis apparatus for preparing radiolabeled drugs, characterized in that, It includes a feeding unit (9), a centrifugal assembly (3), a material end control valve assembly (4), a product end control valve (5), a product collector (6), and a waste liquid collector (7). The feeding unit (9) is used to store raw material reagents or radionuclide-labeled drug stock solution and to deliver the raw material reagents or radionuclide-labeled drug stock solution to the centrifuge assembly (3); The centrifugation assembly (3) is used to prepare a radionuclide-labeled drug stock solution using the raw materials and reagents supplied by the feeding unit (9) and to centrifuge the prepared radionuclide-labeled drug stock solution; or to centrifuge the radionuclide-labeled drug stock solution supplied by the feeding unit (9). The centrifugal assembly (3) includes a centrifugal separation section (32) mounted on a sleeve and a centrifugal control section (31); the centrifugal separation section (32) includes a centrifugal tube (321), a centrifugal cap (322) and a sealing plug (323), the sealing plug (323) is fixed to one end of the centrifugal tube (321), the centrifugal cap (322) is sleeved on the outside of the sealing plug (323) and is rotatably connected to the sealing plug (323); the centrifugal control section (31) is used to drive the centrifugal separation section (32) to rotate; The centrifuge cap (322) includes a centrifuge cap body (3223), a first annular protrusion (3221) and a second annular protrusion (3222) disposed on the centrifuge cap body (3223), the second annular protrusion (3222) being arranged around the first annular protrusion (3221); the sealing plug (323) includes a sealing plug body (3233), a first annular groove (3231) and a second annular groove (3232) disposed on the sealing plug body (3233); the second annular groove (3232) being arranged around the first annular groove (3231); the first annular protrusion (3221) is nested in the first annular groove (3231) and rotatably connected to the first annular groove (3231), the second annular protrusion (3222) is nested in the second annular groove (3232) and rotatably connected to the second annular groove (3232), and a gap is left in the vertical direction; The product collector (6) is used to collect the radionuclide-labeled drug obtained after centrifugation by the centrifugation assembly (3); The waste liquid collector (7) is used to collect the supernatant produced after centrifugation by the centrifugation assembly (3); The centrifugal assembly (3) is selectively connected to the feeding unit (9) via the material end control valve assembly (4), and is also selectively connected to the product collector (6) or the waste liquid collector (7) via the product end control valve (5).

2. The cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to claim 1, characterized in that, The feeding unit (9) includes an injection assembly (1) and a storage assembly (2) mounted on a ferrule. The injection assembly (1) is selectively connected to the centrifugation assembly (3) or the storage assembly (2) via the material end control valve assembly (4) for storing raw material reagents and quantitatively supplying them to the centrifugation assembly (3) or the storage assembly (2). The storage assembly (2) is selectively connected to the injection assembly (1) or the centrifugation assembly (3) via the material end control valve assembly (4) for storing raw material reagents or radionuclide-labeled drug stock solution and supplying them to the centrifugation assembly (3). The storage assembly (2) is also connected to a gas path for supplying gas for pressurizing and stirring or pressurizing and transferring the raw material reagents or radionuclide-labeled drug stock solution, and / or supplying gas via the storage assembly (2) to the centrifugation assembly (3) for pressurizing and transferring the supernatant or radionuclide-labeled drug suspension produced after centrifugation. The feeding unit (9) is also equipped with a heating control unit (10) for heating raw materials, reagents or reaction intermediates.

3. The cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to claim 2, characterized in that, The centrifugal separation section (32) further includes a first conduit (324), a second conduit (325), a third conduit (326), a fourth conduit (327), and a fifth conduit (328); the centrifuge tube (321) includes a vertical section and an inclined section connected to each other, and the sealing plug (323) is fixed to one end of the vertical section of the centrifuge tube (321); one end of the first conduit (324) is connected to the material end control valve assembly (4), and the other end is inserted into the centrifuge cover (322); one end of the second conduit (325) is inserted into the sealing plug. The third conduit (326) is inserted into the centrifuge tube (321) at one end of the plug (323) and at the other end of the product end control valve (5). The fourth conduit (327) is inserted into the sealing plug (323) at one end and is nested and rotated with the other end of the third conduit (326). The other end of the fourth conduit (327) is inserted into the centrifuge tube (321) at one end and at the other end of the fifth conduit (328) at the other end of the centrifuge tube (321) at the bottom of the inclined part. The fifth conduit (328) is embedded in the centrifuge tube (322) at one end and connected to the outside air at the other end.

4. The cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to claim 3, characterized in that, The centrifugation control unit (31) includes a fixing rod (311) and a rotating disk (312). The fixing rod (311) is sleeved on the centrifugation cover (322) for fixing the centrifugation cover (322). The rotating disk (312) is connected to the centrifugation tube (321) for driving the centrifugation tube (321) to centrifuge the radionuclide-labeled drug stock solution.

5. The cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to claim 4, characterized in that, The first annular protrusion (3221) is provided with a first through hole (3224), the first annular groove (3231) is provided with a fourth through hole (3234) corresponding to the first through hole (3224), the second annular protrusion (3222) is provided with a second through hole (3225) and a third through hole (3226), and the second annular groove is provided with a fifth through hole (3235) and a sixth through hole (3236). One end of the first conduit (324) is connected to the material end control valve assembly (4), and the other end is embedded in the second through hole (3225). One end of the second conduit (325) is embedded in the fifth through hole (3235), and the other end passes through the vertical part of the centrifuge tube (321) and extends into the inclined part. One end of the third conduit (326) is connected to the product end control valve (5), and the other end is embedded in the first through hole (3224). One end of the fourth conduit (327) is embedded in the fourth through hole (3234), and the other end passes through the vertical part of the centrifuge tube (321) and extends into the bottom of the inclined part. One end of the fifth conduit (328) is embedded in the third through hole (3226), and the other end is connected to the outside air.

6. The cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to claim 5, characterized in that, The vertical height of the end of the second conduit (325) that extends into the centrifuge tube (321) is higher than the vertical height of the end of the fourth conduit (327) that extends into the centrifuge tube (321).

7. A method for preparing radionuclide-labeled drugs using the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to any one of claims 4 to 6, characterized in that, The radionuclide-labeled drug is a radionuclide-labeled microparticle, and the method includes: The raw materials and reagents are respectively loaded into the feeding unit (9). The raw materials and reagents are raw materials and reagents used to prepare radionuclide labeled microparticles, including radionuclide solution, microparticles to be labeled, pH buffer solution, cleaning solution and preparation medium. The material end control valve assembly (4) is controlled to introduce gas into the liquid storage assembly (2) for pressurization, transfer and mix the raw material reagents, carry out the radionuclide labeling reaction, and start the heating control unit (10) to heat and keep warm, so as to obtain the radionuclide labeled microparticle drug stock solution. Control the material end control valve assembly (4) to add the radionuclide-labeled microparticle drug stock solution to the centrifuge tube (321) of the centrifuge assembly (3); control the rotating disk (312) of the centrifuge assembly (3) to centrifuge the centrifuge tube (321); after centrifugation, control the product end control valve (5) to pressurize the centrifuge tube (321) and transfer the supernatant in the centrifuge tube (321) to the waste liquid collector (7); inject cleaning solution into the centrifuge tube (321) for mixing, centrifuge and remove the supernatant, and then inject the formulation medium to obtain the radionuclide-labeled microparticle suspension; Control the product end control valve (5) to transfer the suspension of radionuclide-labeled microparticles to the product collector (6) for storage.

8. The method for preparing radiolabeled drugs according to claim 7, characterized in that, The particle size in the radionuclide-labeled microparticle suspension is 0.2~100 μm.

9. A method for preparing radionuclide-labeled drugs using the cassette-type synthesis apparatus for preparing radionuclide-labeled drugs according to any one of claims 4 to 6, characterized in that, The radionuclide-labeled drug is a radionuclide-labeled cell, and the method includes: The raw materials and reagents are respectively loaded into the feeding unit (9). The raw materials and reagents are raw materials and reagents used to prepare radionuclide-labeled cells, including cell suspension, radionuclide solution, washing solution and preparation medium. Control the material end control valve assembly (4) to add cell suspension to the centrifuge tube (321) of the centrifuge assembly (3); control the rotating disk (312) of the centrifuge assembly (3) to centrifuge the centrifuge tube (321); after centrifugation, control the product end control valve (5) to pressurize the centrifuge tube (321) and transfer the supernatant in the centrifuge tube (321) to the waste liquid collector (7). Control the material end control valve assembly (4), add radioactive nuclide solution to centrifuge tube (321) for reaction, add washing liquid and mix evenly, centrifuge multiple times and remove supernatant, add preparation medium and mix evenly to obtain radioactive nuclide labeled cell suspension; Control the product end control valve (5) to pressurize the centrifuge tube (321) by introducing gas, and transfer the radionuclide-labeled cell suspension to the product collector (6) for storage.

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