Automatic synthesis equipment for multi-batch 18F-FDG drugs

Abstract

The utility model discloses automatic synthesis equipment for multi-batch 18F-FDG drugs. The automatic synthesis equipment comprises a plurality of activity probes, a control module, a negative pressure device, a clamping sleeve, an air blowing device and a reaction device, wherein the control module is used for controlling on-off of valves on a pipeline and the clamping sleeve; the air blowing device and the reaction device are connected with the clamping sleeve through the pipeline; a plurality of solution bottles, a C18 column, a plurality of aluminum oxide columns and an injector are arranged on the clamping sleeve; the plurality of solution bottles provide a solution for activating the C18 column and cleaning the pipeline, and the solution for activating the C18 column is extracted by the injector and passes through the C18 column, so that the C18 column is activated; the reaction device is used for raw material reaction and provided with a temperature control device; and pipelines of the equipment are cleaned through the cleaning bottle and the blowing device, so that 18F-FDG can be synthesized in multiple batches. According to the scheme, all control valves and pipelines are connected to realize full-airtight controllable reaction, continuous multiple drug synthesis is realized, and the production efficiency of drugs is not influenced.

Description

Technical Field

[0001] This utility model belongs to the field of radiopharmaceutical preparation, specifically relating to a multi-batch... 18 Automated synthesis equipment for F-FDG drugs. Background Technology

[0002] Positron emission tomography (PET) is an advanced clinical imaging technique in nuclear medicine, offering advantages such as non-invasiveness, high sensitivity, high specificity, and good safety. It is a distinctive modern molecular imaging technology. Compared to conventional imaging examinations (ultrasound, CT, MRI, etc.), PET can screen for lesions throughout the body in a single procedure, enabling more sensitive, accurate, and early detection of lesions. It is considered one of the best methods for diagnosing and guiding cancer treatment. It is now widely used in the diagnosis and differential diagnosis of various diseases, disease assessment, efficacy evaluation, organ function research, and new drug development. By detecting changes in the distribution, quantity, and function of biomarkers within the body using targeted radiopharmaceuticals, it achieves the goal of non-invasive detection of pathological changes at the in vivo level. Radiopharmaceuticals are key to the functionality of PET; however, due to their short half-life, these drugs need to be prepared before use.

[0003] 18 F-FDG is easily absorbed by tumor cells, and can be detected through testing. 18 F-FDG imaging on PET-CT can detect primary and metastatic lesions of tumors throughout the body at an early stage, accurately determine their benign or malignant nature, and thus correctly guide clinical treatment decisions. It is a common and typical radiopharmaceutical. 18 F-FDG is a short-lived radionuclide with a half-life of only 110 minutes. Sometimes it needs to be produced multiple times a day to meet clinical needs. When used in large quantities, multiple synthesis devices are required to facilitate production in batches as needed, which increases production costs.

[0004] The manual synthesis of radiopharmaceuticals presents challenges such as operator exposure to significant radiation, susceptibility of synthesis efficiency to human error, and inconsistent yields. Therefore, automated radiopharmaceutical synthesis instruments have been developed and are now widely used.

[0005] Currently on the market 18 The F-FDG drug synthesis system has the following main problems:

[0006] 1. Current 18 The F-FDG drug synthesis instrument uses compressed air cooling. The reaction vessel of the synthesis instrument requires a negative pressure environment. Using compressed air cooling poses a risk of leakage of air containing radioactive materials, which could cause radiation damage to the experimental personnel.

[0007] 2. Current 18 F-FDG drug synthesis instruments mostly adopt a disposable ferrule design. The solid phase extraction column C18 is usually activated before installation. The advantage of this is that it can ensure that the C18 column is fully activated. The disadvantage is that it is easy to be contaminated before installation and it is labor-intensive. The C18 column plays a vital role in the entire drug synthesis process. If the C18 column is contaminated, it will cause irreversible results.

[0008] Therefore, it is necessary to develop a synthesis method that is highly efficient, safe, stable, and can meet the requirements of multiple batches. 18 A multifunctional automated synthesis instrument for F-FDG drug synthesis is a technical problem that needs to be solved by those skilled in the art. Utility Model Content

[0009] To address the problems existing in current synthesis technologies, this utility model discloses a method for synthesizing... 18 F-FDG drug multi-batch automated synthesis equipment to achieve 18 This invention enables the synthesis of F-FDG drugs in multiple batches with high efficiency and stable safety. To achieve the above objectives, the present invention adopts the following technical solution:

[0010] A multi-batch 18 An automated synthesis device for F-FDG drugs includes: several activity probes, a control module, a negative pressure device, a ferrule, and tubing connected to the ferrule. 18 F output device, air blowing device, waste liquid bottle, product collection bottle, reaction device and oxygen water recovery bottle;

[0011] The aforementioned activity probes are used for real-time... 18 F activity;

[0012] The control module is used to control the opening and closing of valves on pipelines and ferrules;

[0013] The negative pressure device is connected to the sealed reaction device via a pipeline;

[0014] The ferrule is equipped with several solution bottles, a C18 column for hydrolyzing and displacing the reaction products, several alumina columns for purifying the products, and a syringe for drawing and ejecting the solution from the solution bottles.

[0015] The plurality of solution bottles respectively provide solutions for activating the C18 column, the raw materials for the reaction, and cleaning the tubing, wherein the solution for activating the C18 column is drawn through the C18 column by the syringe to activate the C18 column.

[0016] The 18 The F output device is used to provide... 18 Solution of F ions;

[0017] The blowing device is used to blow gas into the pipeline;

[0018] The reaction apparatus is used to carry out the reaction of raw materials and has a temperature control device;

[0019] The equipment's piping is cleaned using the cleaning bottle and air blowing device, enabling multi-batch synthesis. 18 F-FDG.

[0020] Furthermore, the ferrule includes a plurality of n-row three-way valves, which are used to adjust the flow of the pipeline at the corresponding valve port by rotating the three-way valves. The n-row three-way valves are connected by pipelines, and n is at least 2.

[0021] Furthermore, the device also includes a waste liquid bottle and a product collection bottle; the waste liquid bottle is used to collect waste liquid generated during the operation of the device; the product collection bottle is connected to the sample outlet of the plurality of alumina columns through a pipeline.

[0022] Furthermore, the plurality of activity probes are respectively disposed in the... 18 On the F output device, product collection bottle, C18 column, and reaction apparatus, for real-time monitoring 18 The activity of F.

[0023] Furthermore, the reaction apparatus includes: a reaction vessel and an activity probe and a temperature control device disposed thereon; the temperature control device includes: a temperature control unit, a heat-conducting pot body and a dry heating component and a water circulation cooling system disposed thereon, the heat-conducting pot body being used to place the reaction vessel and being made of aluminum alloy; the temperature control unit being used to monitor the real-time temperature inside the reaction vessel; the water circulation cooling system includes: a heat dissipation circulating water channel, a radiator and a circulating water pump, the heat dissipation circulating water channel being in contact with the reaction vessel, the radiator being connected to the heat dissipation circulating water channel, and the circulating water pump driving the coolant to circulate in the radiator and the heat dissipation circulating water channel.

[0024] Furthermore, the aforementioned 18 The F-output device includes a cyclotron, a transfer bottle with an activity probe, an oxygen recovery bottle, and a... 18 A QMA solid-phase extraction column for adsorption of F ions and for removing the adsorbed ions from the QMA solid-phase extraction column. 18 The eluent bottle for F-ion elution; the cyclotron-generated eluent containing F-ions. 18 H2 of F ions 18 O2 solution enters a connected transfer bottle through a pipeline. The oxygen recovery bottle is connected to a negative pressure device and a QMA column through a pipeline. The negative pressure device generates negative pressure in the pipeline, causing the oxygen in the transfer bottle to... 18 H2 of F ions 18The O solution flows into the oxygen recovery bottle after passing through the QMA column, and then the eluent is drawn through the syringe and passed through the QMA solid-phase extraction column. The solution adsorbed on the QMA solid-phase extraction column... 18 F ions are eluted into the syringe.

[0025] Furthermore, the solution bottle includes: an activator bottle for activating the C18 column, a raw material bottle, and a cleaning bottle for cleaning the pipeline.

[0026] Furthermore, the raw material bottle includes: an acetonitrile solution bottle, a precursor solution bottle, a NaOH solution bottle, and a buffer solution bottle; the activator is ethanol; the cleaning bottle contains water; and the precursor solution is a mixed solution of trifluoromannose and acetonitrile.

[0027] Furthermore, the gas blown by the blowing device is an inert gas, and the pipelines of the blowing device and the negative pressure device are equipped with a flow controller, a proportional valve and a pinch valve to control the gas output of the blowing device or the negative pressure generated by the operation of the negative pressure device.

[0028] Furthermore, the control module is also used to control the temperature control device and the syringe pumping.

[0029] The beneficial effects of this utility model are as follows:

[0030] (1) This invention automates the activation of the C18 column using a disposable sleeve, with the activator drawn up by a syringe and delivered to the C18 column for thorough moistening. Compared to the traditional method of external manual activation before installation, this invention enables the activation of the C18 column during instrument use, maintaining a long-term moist state of the drug, effectively ensuring the normal adsorption of radioactive ions, and preventing the C18 column from drying out or becoming contaminated.

[0031] (2) The water circulation cooling system used in this utility model is more stable than air cooling and will not cause radioactive pollution, thus ensuring the safety of experimental personnel.

[0032] (3) Implementation of this utility model 18 The multi-batch synthesis of F-FDG drugs is carried out in a fully gas-tight and controllable manner through valve and pipeline connections. The pipeline cleaning and cooling are controlled by the flow rate of gas and liquid. The drug can be synthesized continuously multiple times without changing the reaction equipment and without affecting the drug production efficiency. It has the characteristics of high synthesis efficiency and safety and stability. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of a specific embodiment of the synthesis equipment described in this utility model;

[0034] In the diagram: P1, eluent bottle; P2, acetonitrile solution bottle; P3, precursor solution bottle; P4, ethanol solution bottle; P5, buffer solution bottle; P6, waste liquid bottle; P7, oxygen recovery bottle; P8, transfer bottle; P9, cleaning bottle; P10, reaction vessel; P11, product collection bottle; Z1, syringe; Z2, NaOH syringe; A1, activity probe; A2, C18 column; A3, alumina column; A4, temperature control device; A5, filter membrane; A6, QMA column. Detailed Implementation

[0035] The present invention will be further described below with reference to specific embodiments. The following embodiments are for illustrative purposes only and are not intended to limit the scope of application of the present invention.

[0036] One example of this utility model is a multi-batch... 18 An automated synthesis device for F-FDG drugs includes: several activity probes A1, a control module, a negative pressure device, a ferrule, and tubing connected to the ferrule. 18 The F output device, the blowing device, the reaction device, and the oxygen water recovery bottle P7; the several activity probes A1 are used for real-time... 18 The activity of F; the control module is used to control the opening and closing of valves on the pipeline and the ferrule; the negative pressure device is connected to the sealed reaction device through a pipeline; the ferrule is equipped with several solution bottles, a C18 column A2 for hydrolyzing and displacing the reaction product, several alumina columns A3 for purifying the product, and a syringe Z1 for drawing and ejecting the solution from the solution bottles; the several solution bottles respectively provide solutions for activating the C18 column A2, the raw materials for the reaction, and cleaning the pipeline, wherein the solution for activating the C18 column A2 is drawn through the syringe Z1 and passes through the C18 column A2 to achieve the activation of the C18 column A2; the... 18 The F output device is used to provide... 18 A solution of F ions; the blowing device is used to blow inert gas into the pipeline; the reaction device is used to carry out the raw material reaction and has a temperature control device A4; the pipeline of the equipment is cleaned by the cleaning bottle P9 and the blowing device, enabling multi-batch synthesis. 18 F-FDG.

[0037] Example 1:

[0038] The rinsing solution and buffer solution used in this embodiment are conventional solutions in the art;

[0039] like Figure 1 This embodiment includes: four activity probes A1, a control module, a negative pressure device, and a ferrule. 18 F output device, air blowing device, waste liquid bottle P6, product collection bottle P11 and reaction device;

[0040] The sleeve is equipped with a limiting structure that fits the mouth of the solution bottle. The limiting structure can improve the docking accuracy. The limiting structure can be a limiting groove or a limiting protrusion. An annular sealing gasket is provided within the limiting structure to improve the fit with the bottle opening. The sleeve specifically comprises five five-way three-way valves: the first five-way three-way valve (numbered 1-5), the second five-way three-way valve (numbered 6-10), the third five-way three-way valve (numbered 11-15), the fourth five-way three-way valve (numbered 16-20), and the fifth five-way three-way valve (numbered 21-25). The sleeve is equipped with an activator for activating the C18 column A2, a raw material bottle and a cleaning bottle P9 containing pure water, the C18 column A2 for hydrolyzing and displacing the reaction product, four alumina columns A3 for purifying the product, and two syringes Z1 for drawing and dispensing the solution from the solution bottle. The activator for activating the C18 column A2 is drawn through the syringes Z1 and passes through the C18 column A2 to activate it.

[0041] 18 The F output device includes: a cyclotron, a transfer bottle P8, an oxygen recovery bottle P7, and a... 18 The QMA solid-phase extraction column for F ion adsorption, namely QMA column A6, and the method for adsorbing F ions on the QMA solid-phase extraction column. 18 F-ion elution eluent bottle P1;

[0042] The reaction apparatus includes: a reaction vessel P10 and a temperature control device A4;

[0043] The raw material bottles include: acetonitrile solution bottle P2, precursor solution bottle P3, syringe Z2 containing NaOH solution, and buffer solution bottle P5; the activator is ethanol; the precursor solution is a mixed solution of trifluoromannose and acetonitrile.

[0044] Positions 1-5 of the first five-way three-port valve are connected, from left to right, to the QMA solid-phase extraction column, the aeration device, the acetonitrile solution bottle P2, the syringe Z1, and the precursor solution bottle P3; positions 6-10 of the second five-way three-port valve are connected, from left to right, to the reaction vessel P10, position 20 of the third five-way three-port valve, the ethanol activator (ethanol solution) bottle P4, the buffer solution bottle P5, and the syringe Z2 containing NaOH solution; positions 11-15 of the third five-way three-port valve are connected, from left to right, to the C18 column A2, the syringe Z1, and the precursor solution bottle P3. 1. C18 column A2, C18 column A2 at position 13, and the rightmost end of the fifth five-way three-way valve are connected; positions 16-20 of the fourth five-way three-way valve are connected from left to right to the QMA solid-phase extraction column at position 1, the eluent bottle P1, the aeration device, the cleaning bottle P9 containing pure water, and position 7 of the second five-way three-way valve; of positions 21-25 of the fifth five-way three-way valve, positions 22-25 are connected to alumina columns A3 respectively, and position 21 is connected to alumina columns A3 at positions 22-25; the product The product collection bottle P11 is connected to the left end of the fifth five-way valve, and the inlet of the product collection bottle P11 is equipped with a filter membrane P10; the waste liquid bottle P6 is connected to the right end of the third five-way valve; the cyclotron is connected to the transfer bottle P8, the transfer bottle P8 is connected to the left end of the fourth five-way valve, the oxygen water recovery bottle P7 is connected to the left end of the first five-way valve, and is also connected to the negative pressure device; the reaction vessel P10 is also connected to the negative pressure device, and the temperature control device A4 includes a temperature control unit, a heat-conducting pot body, and a filter membrane P10. The reactor includes a dry heating element and a water circulation cooling system. The heat-conducting pot body is used to house the reactor P10 and is made of aluminum alloy. An insulation layer made of polytetrafluoroethylene is provided on the outside of the pot body. The temperature control unit is used to monitor the real-time temperature inside the reactor P10. The water circulation cooling system includes a heat dissipation circulating water channel, a radiator, and a circulating water pump. The heat dissipation circulating water channel is in contact with the reactor P10, and the radiator is connected to the heat dissipation circulating water channel. The circulating water pump drives the coolant to circulate in the radiator and the heat dissipation circulating water channel.

[0045] like Figure 1 As shown, the various components are connected through the pipelines. The pinch valves are installed on the two pipelines connected to the reactor P10, the two pipelines connected to the negative pressure device, the two pipelines connected to the air blowing device, and the four pipelines connected to the four eluent bottles P1 respectively. Specifically, they are pinch valves K1-K10.

[0046] The activity probe A1 is respectively installed on the transfer bottle P8, the C18 column A2 at position 11, the reaction vessel P10, and the product collection bottle P11, so as to detect the activity in real time. 18 F activity;

[0047] The control module is used to control the pushing and pulling of the syringe Z1 and the NaOH syringe Z2, to switch the valves on the five-way three-way valve to control the on / off of each pipeline, and to control the temperature of the temperature control device A4; the gas blowing device is equipped with a flow controller and a proportional valve to control the nitrogen flow rate blown into the pipeline; the negative pressure device is equipped with a flow controller and a proportional valve and the negative pressure in the pipeline is adjustable through a vacuum pump.

[0048] Example 2:

[0049] According to the automated synthesis equipment provided in Example 1, its working process is as follows:

[0050] S1. Preparation before synthesis

[0051] Pre-activate the QMA solid-phase extraction column and four alumina columns in advance, then install the activated QMA column A6 at position 1, and install the four alumina columns A3 at positions 22-25, and check the equipment.

[0052] S2. Activation of the C18 solid-phase extraction column

[0053] Activation of the C18 solid-phase extraction column: The syringe Z1 at position 12 extracts ethanol from the ethanol solution bottle P4 at position 8, rotates the five-way three-way valve, and passes the ethanol at position 8 through the C18 column A2 at position 11 to fully moisten the C18 column A2. Then, the syringe Z1 at position 12 pushes out the ethanol, passes through the C18 column A2 at position 13, and then enters the waste liquid bottle P6, and the activation of the C18 column A2 is completed. After the activation of the C18 column A2, use the syringe Z1 at position 12 to draw pure water from the cleaning bottle P9 at position 19 through the C18 column A2 at position 11, and then push it out through the C18 column A2 at position 13 and enter the waste liquid bottle P6 to clean the two C18 columns A2. Nitrogen is passed through at position 18 to dry the residual in the pipeline to avoid pipeline contamination.

[0054] S3. 18 Capture of F

[0055] Start the vacuum pump at the negative pressure device to form a negative pressure in the pipeline. Under the drive of the negative pressure, draw the H2 18 containing F ions from the transfer bottle P8, and make it pass through the QMA solid-phase extraction column at position 1. 18 The F ions will be adsorbed on the QMA solid-phase extraction column, and the remaining H2 18 O liquid will enter the oxygen water recovery bottle P7. By adjusting the negative pressure, control the flow rate of H2 18 O, and optimize the H2 18 O in 18 O 18The adsorption effect of F by the QMA solid phase extraction column, the activity probe A1 located at the transfer bottle P8 records the initial activity before the reaction, and the activity probe A1 located at the reaction vessel P10, C18 column A2 and product collection bottle P11 records the activity information of the solution during the experiment. It can stop the preparation of reactants that do not meet the activity requirements in time, so as to improve the preparation efficiency and reduce unnecessary waste.

[0056] S4. 18 F's rinse

[0057] Injector Z1 at position 4 draws any eluent connected to position 17. The drawn eluent passes through the QMA solid-phase extraction column at position 1 and is then pushed into the reaction vessel P10. The eluent adsorbed by the QMA solid-phase extraction column at position 1... 18 F is rinsed into the reactor. At the same time, temperature control device A4 starts heating until the set temperature is reached. Nitrogen gas continues to be introduced through position 2, and the nitrogen gas blown out through position 18 is used to blow the residual liquid in the pipeline into the reactor to reduce the amount of residue.

[0058] S5. Evaporation to remove water

[0059] Heat reactor P10 while simultaneously activating negative pressure and nitrogen purging at position 2. Use syringe Z1 at position 4 to draw the precursor solution (a mixture of trifluoromannose and acetonitrile) from position 5 and inject it into reactor P10. Continue heating, and purge reactor P10 with nitrogen and negative pressure at position 2 to purge it, allowing any remaining liquid in reactor P10 to evaporate rapidly until reactor P10 is dry and free of residue.

[0060] S6. Reaction

[0061] Injector Z1 at position 4 draws the precursor solution (a mixture of trifluoromannose and acetonitrile) from position 5 and pushes it into reactor P10. Heating continues, nitrogen and negative pressure are turned off, and clamp valves K1 and K2 of reactor P10 are closed. This continues until the reaction time ends, then heating is turned off, and the water circulation cooling system of temperature control device A4 is turned on.

[0062] S7. Top Pillar

[0063] Injector Z1 at position 12 draws pure water from position 19 and pushes it into reactor P10. Then, injector Z1 at position 12 draws the water back through column A2 at position 11. Repeat this process to ensure that the reactants in reactor P10 are fully adsorbed onto column A2 at position C18. The used pure water is then discharged into waste bottle P6.

[0064] S8. Hydrolysis

[0065] NaOH solution is pushed out of NaOH syringe Z2 at position 10 through column A2 of C18 at position 11, so that column A2 of C18 is filled with NaOH solution. Then, valves at positions 10 and 11 are closed, so that the NaOH solution completely submerges column A2 of C18 for a period of time, thereby carrying out the hydrolysis reaction.

[0066] S9. Post-reaction washing

[0067] Nitrogen gas is introduced to pressurize the system at position 2. Syringe Z1 at position 12 draws pure water from position 19, which is then pumped through column A2 (C18) at position 11 and into waste liquid bottle P6. Nitrogen gas is introduced to position 18, which is then blown through column A2 (C18) at position 11 into waste liquid bottle P6, thus cleaning the pipeline.

[0068] S10. Washing.

[0069] Nitrogen gas is introduced to pressurize the buffer solution at position 2. The buffer solution is drawn from syringe Z1 at position 12 and passed through column A2 (C18) at position 11. Syringe Z1 is then pushed out and passed through column A2 (C18) at position 13 to remove unreacted intermediates and purify the product. The product is then passed through any alumina column A3 for further purification before entering the product collection bottle P11.

[0070] S11. Rinse after reaction

[0071] Injector Z1 at position 12 draws pure water from position 19 and injects it into reactor P10. Then, injector Z1 is withdrawn and the water is injected into waste bottle P6. Nitrogen gas is introduced at position 18, passing through column A2 (C18) at position 11 and being blown into waste bottle P6. Injector Z1 at position 12 draws pure water from position 19, passes through column A6 (QMA) at position 1, and injects it into waste bottle P6. Injector Z1 is emptied and the water is injected into waste bottle P6. Nitrogen gas is introduced at position 18, passing through column A6 (QMA) at position 1, and being blown into waste bottle P6. Injector Z1 at position 4 draws acetonitrile solution and injects it into reactor P10. Reactor P10 is heated, and nitrogen gas is introduced at position 2 under negative pressure until reactor P10 is completely dried, ready for the next batch. 18 In this embodiment, a total of four batches of F-FDG drug can be prepared. 18 F-FDG drug preparation.

[0072] In the above steps, each unit of the control module is connected to the computer, and the software program is used to control the rotation of the three-way valve, the opening and closing of the gas pipeline and the liquid pipeline, the heating and cooling of the P10 reactor, and the reading of temperature and radiation activity data during the synthesis process.

[0073] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A multi-batch 18 An automated synthesis apparatus for F-FDG drugs, characterized by, The application relates to a device for synthesizing and purifying a product, which comprises the following parts: Several activity probes, control modules, negative pressure devices, sleeves and pipelines connected with the sleeves 18 F output device, blowing device, reaction device; the several activity probes are used for monitoring the activity of F in real time 18 F The control module is used for controlling the opening and closing of valves on the pipeline and the sleeve; The negative pressure device is connected with the reaction device through a pipeline; A plurality of solution bottles, a C18 column for hydrolysis and replacement of a reaction product, a plurality of alumina columns for purifying a product and a syringe for extracting and pushing out solutions in the solution bottles are arranged on the sleeve; The plurality of solution bottles respectively provide solutions for activating the C18 column, raw materials for reaction and cleaning the pipeline, wherein the solution for activating the C18 column is extracted through the C18 column by the syringe to realize activation of the C18 column; The 18 F output device is used to provide a solution containing 18 F ions; The blowing device is used for blowing inert gas into the pipeline; The reaction device is used for raw material reaction and has a temperature control device; Cleaning of the equipment lines by solution bottles and blowing devices allows to realize multi-batch synthesis 18 F-FDG.

2. The automated synthesis apparatus according to claim 1, characterized by The sleeve comprises a plurality of n-row three-way valves, the opening and closing of the pipeline corresponding to the valve ports are adjusted by rotating the three-way valves, the n-row three-way valves are connected through pipelines, and n is at least 2.

3. The automated synthesis apparatus according to claim 1, wherein, The device further comprises a waste liquid bottle and a product collection bottle; the waste liquid bottle is used for collecting waste liquid generated in the working process of the device; and the product collection bottle is connected with sample outlets of the plurality of alumina columns through a pipeline.

4. The automated synthesis apparatus according to claim 3, wherein The several activity probes are respectively arranged on the 18 F output device, product collection bottle, C18 column and reaction device.

5. The automated synthesis apparatus according to claim 1, wherein, The reaction device comprises a reaction kettle and an activity probe and a temperature control device arranged on the reaction kettle; the temperature control device comprises a temperature control unit, a heat-conducting kettle body and dry heating components and a water circulation cooling system arranged on the heat-conducting kettle body; the heat-conducting kettle body is used for placing the reaction kettle and is made of aluminum alloy material; the temperature control unit is used for monitoring the real-time temperature in the reaction kettle; and the water circulation cooling system comprises a heat dissipation circulating water channel, a cooling radiator and a circulating water pump; the heat dissipation circulating water channel abuts against the reaction kettle; the cooling radiator is connected with the heat dissipation circulating water channel; and the circulating water pump drives the cooling liquid to circulate in the cooling radiator and the heat dissipation circulating water channel.

6. The automated synthesis apparatus according to claim 1, wherein, The 18 The F output device comprises a cyclotron, a transfer bottle with an activity probe, an oxygen water recovery bottle, a negative pressure device, a QMA solid phase extraction column for adsorbing ions, and an eluent bottle for eluting the ions adsorbed on the QMA solid phase extraction column. 18 The F output device comprises a cyclotron, a transfer bottle with an activity probe, an oxygen water recovery bottle, a negative pressure device, a QMA solid phase extraction column for adsorbing ions, and an eluent bottle for eluting the ions adsorbed on the QMA solid phase extraction column. 18 The F output device comprises a cyclotron, a transfer bottle with an activity probe, an oxygen water recovery bottle, a negative pressure device, a QMA solid phase extraction column for adsorbing ions, and an eluent bottle for eluting the ions adsorbed on the QMA solid phase extraction column. 18 The H2 18 O solution generated by the cyclotron containing F ions enters the transfer bottle connected thereto through a pipeline, the oxygen water recovery bottle is connected with the negative pressure device through a pipeline and also connected with the QMA column through a pipeline.

7. The automated synthesis apparatus according to claim 1, wherein, The solution bottles comprise an activator bottle for activating the C18 column, a raw material bottle and a cleaning bottle for cleaning the pipeline.

8. The automated synthesis apparatus according to claim 7, wherein, The raw material bottle comprises an acetonitrile solution bottle, a precursor solution bottle, a NaOH solution bottle and a buffer solution bottle.

9. The automated synthesis apparatus according to claim 1, wherein, The inert gas is nitrogen, flow controllers, proportional valves and pinch valves are arranged on the pipelines connected with the blowing device and the negative pressure device, and the flow controllers, the proportional valves and the pinch valves are used for controlling the gas output of the blowing device or the negative pressure generated by the negative pressure device.

10. The automated synthesis apparatus according to claim 1, wherein, The control module is further used for controlling the temperature control device and the syringe.

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