1. A synthetic system for preparing positron medicine 18F-FDG is characterized by comprising an F18 collector and a closed reaction tube connected with the collector through a pipeline, wherein the reaction tube is provided with a heating device, the bottom of the reaction tube is provided with a fifth control valve,

the reaction tube is also connected with a first recovery bottle, a raw material input device and an output device;

the raw material input device comprises a first multi-way valve, a first raw material propeller and a second raw material propeller, wherein the first raw material propeller and the second raw material propeller are connected with the first multi-way valve;

the output device comprises a first three-way valve connected with the reaction pipe and a transfer bottle connected with the first three-way valve, the transfer bottle is connected with a third raw material propeller, and a raw material bottle of the third raw material propeller is used for storing water for injection;

the first three-way valve is also connected with a collecting branch, the collecting branch comprises a second multi-way valve 10 connected with the first three-way valve, a third multi-way valve 11 connected with the second multi-way valve, a fourth multi-way valve 12 connected with the third multi-way valve and a fifth multi-way valve 14 connected with the fourth multi-way valve, a plurality of first purifying columns 28 are connected in parallel between the second multi-way valve and the third multi-way valve, the fifth multi-way valve is connected with a plurality of second purifying columns, and each second purifying column is connected with a product collecting bottle;

the second multi-way valve is also connected with a fourth raw material propeller, and a raw material bottle of the fourth raw material propeller is used for storing a sodium hydroxide solution;

the synthesis system also comprises a blowing device connected with the reaction tube, the first multi-way valve, the second multi-way valve and the transfer bottle, and a control valve is arranged on the connecting pipeline.

2. The synthetic system for the preparation of a positron emitting drug 18F-FDG as claimed in claim 1 wherein: the F18 collector comprises a rotatable multi-channel change-over valve and a fifth raw material propeller, and also comprises a target water input pipe, a target water output pipe and a QMA (quality model analysis) column which is connected with the target water output pipe in series, wherein the outlets of the target water input pipe, the target water output pipe and the fifth raw material propeller are positioned at different valve ports of the multi-channel change-over valve; and the raw material bottle of the fifth raw material propeller is used for storing the aminopolyether acetonitrile solution containing potassium carbonate.

3. The synthetic system for the preparation of a positron emitting drug 18F-FDG as claimed in claim 2 wherein: the blowing device is connected with at least one valve port of the multi-channel conversion valve.

4. The synthetic system for the preparation of a positron emitting drug 18F-FDG as claimed in claim 1 wherein: and a second three-way valve is connected between the fourth multi-way valve 12 and the fifth multi-way valve 14, and the second three-way valve is connected with a waste liquid recovery bottle.

5. The synthetic system for the preparation of a positron emitting drug 18F-FDG as claimed in claim 1 wherein: the reaction tube and the second multi-way valve are connected with a blowing device through a gas flow controller.

6. The synthetic system for the preparation of a positron emitting drug 18F-FDG according to any one of claims 1 to 5, wherein: and the PLC is in control connection with each three-way valve, the multi-way valve, the raw material propeller and the blowing device.

Background

Positron Emission Tomography (PET) is a clinical and practical medical imaging means, and the aim of noninvasive detection of pathological changes at the living body level is achieved by detecting the changes of the distribution, the quantity and the functions of biomarkers in a human body through targeted radiopharmaceuticals. Radiopharmaceuticals are the key to achieving the functions of PET, and the radiopharmaceuticals need to be prepared before use due to short half-life. The radiopharmaceuticals were initially synthesized manually, which has the problem that the operators were exposed to more radiation, the efficiency of the drug synthesis was also susceptible to human factors, and the yield was unstable. Automated radiopharmaceutical synthesis equipment has therefore been developed and widely used.

18F-FDG is easy to be absorbed by tumor cells, the primary and metastatic focuses of the whole body tumor can be found at early stage by detecting 18F-FDG in PET-CT imaging, and the benign and malignant tumors can be accurately judged, so that the clinical treatment decision can be correctly guided.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention discloses a synthesis system for preparing a positron medicine 18F-FDG.

The invention relates to a synthesis system for preparing a positron medicine 18F-FDG, which comprises an F18 collector and a closed reaction tube connected with the collector through a pipeline, wherein the reaction tube is provided with a heating device, the bottom of the reaction tube is provided with a fifth control valve,

the reaction tube is also connected with a first recovery bottle, a raw material input device and an output device;

the raw material input device comprises a first multi-way valve, a first raw material propeller and a second raw material propeller, wherein the first raw material propeller and the second raw material propeller are connected with the first multi-way valve;

the output device comprises a first three-way valve connected with the reaction pipe and a transfer bottle connected with the first three-way valve, the transfer bottle is connected with a third raw material propeller, and a raw material bottle of the third raw material propeller is used for storing water for injection;

the first three-way valve is also connected with a collecting branch, the collecting branch comprises a second multi-way valve 10 connected with the first three-way valve, a third multi-way valve 11 connected with the second multi-way valve, a fourth multi-way valve 12 connected with the third multi-way valve and a fifth multi-way valve 14 connected with the fourth multi-way valve, a plurality of first purifying columns 28 are connected in parallel between the second multi-way valve and the third multi-way valve, the fifth multi-way valve is connected with a plurality of second purifying columns, and each second purifying column is connected with a product collecting bottle;

the second multi-way valve is also connected with a fourth raw material propeller, and a raw material bottle of the fourth raw material propeller is used for storing a sodium hydroxide solution;

the synthesis system also comprises a blowing device connected with the reaction tube, the first multi-way valve, the second multi-way valve and the transfer bottle, and a control valve is arranged on the connecting pipeline.

Preferably: the F18 collector comprises a rotatable multi-channel change-over valve and a fifth raw material propeller, and also comprises a target water input pipe, a target water output pipe and a QMA (quality model analysis) column which is connected with the target water output pipe in series, wherein the outlets of the target water input pipe, the target water output pipe and the fifth raw material propeller are positioned at different valve ports of the multi-channel change-over valve; and the raw material bottle of the fifth raw material propeller is used for storing the aminopolyether acetonitrile solution containing potassium carbonate.

Preferably: the blowing device is connected with at least one reaction position of the multi-channel switching valve.

Preferably: and a second three-way valve is connected between the fourth multi-way valve 12 and the fifth multi-way valve 14, and the second three-way valve is connected with a waste liquid recovery bottle.

Preferably: the reaction tube and the second multi-way valve are connected with a blowing device through a gas flow controller.

Preferably: and the PLC is in control connection with each three-way valve, the multi-way valve idle device, the raw material propeller and the blowing device.

The synthesis system for preparing the positron medicine 18F-FDG realizes full-airtight controllable reaction through connection of each valve and each pipeline, utilizes the blowing device to clean and cool the pipelines, can realize continuous and repeated medicine synthesis under the condition of not opening the reaction tube and does not influence the production quality of the medicine.

Drawings

FIG. 1 is a schematic diagram of one embodiment of a synthesis system according to the present invention.

1-a multichannel conversion valve, 2-a fifth raw material pusher, 3-a first raw material pusher, 4-a second raw material pusher, 5-a third raw material pusher, 6-a fourth raw material pusher, 7-a first recovery cylinder, 8-a first multi-way valve, 9-a first three-way valve, 10-a second multi-way valve, 11-a third multi-way valve, 12-a fourth multi-way valve, 13-a second three-way valve, 14-a fifth multi-way valve, 15-a first control valve, 16-a second control valve, 17-a third control valve, 18-a fourth control valve, 19-a fifth control valve, 23-a third recovery cylinder, 25-a second recovery cylinder, 26-a product cylinder, 27-a QMA cylinder, 28-a first purification cylinder, 29-a second purification cylinder, 32-gas flow controller, 34-sterile filter membrane.

Detailed Description

The following provides a more detailed description of the present invention.

The synthesis system for preparing the positron medicine 18F-FDG comprises an F18 collector and a closed reaction tube connected with the collector through a pipeline, wherein the reaction tube is provided with a heating device, the bottom of the reaction tube is provided with a fifth control valve,

the reaction tube is also connected with a raw material input device and an output device; and is connected with a first recovery bottle through a control valve;

the raw material input device comprises a first multi-way valve, a first raw material propeller and a second raw material propeller, wherein the first raw material propeller and the second raw material propeller are connected with the first multi-way valve;

the output device comprises a first three-way valve connected with the reaction pipe and a transfer bottle connected with the first three-way valve, the transfer bottle is connected with a third raw material propeller, and a raw material bottle of the third raw material propeller is used for storing water for injection;

the first three-way valve is also connected with a collecting branch, the collecting branch comprises a second multi-way valve 10 connected with the first three-way valve, a third multi-way valve 11 connected with the second multi-way valve, a fourth multi-way valve 12 connected with the third multi-way valve and a fifth multi-way valve 14 connected with the fourth multi-way valve, a plurality of first purifying columns 28 are connected in parallel between the second multi-way valve and the third multi-way valve, the fifth multi-way valve is connected with a plurality of second purifying columns, and each second purifying column is connected with a product collecting bottle;

the second multi-way valve is also connected with a fourth raw material propeller, and a raw material bottle of the fourth raw material propeller is used for storing a sodium hydroxide solution;

the synthesis system also comprises a blowing device connected with the reaction tube, the first multi-way valve, the second multi-way valve and the transfer bottle, and a control valve is arranged on the connecting pipeline.

Wherein the F18 collector is used for eluting F18 ions, and after the cyclotron targeting is finished, target water enters the F18 collector, in the specific embodiment shown in fig. 1, the F18 collector includes a rotatable multi-channel switching valve and a fifth raw material propeller, and further includes a target water input pipe, a target water output pipe, and a QMA column connected in series to the target water output pipe, and outlets of the target water input pipe, the target water output pipe, and the fifth raw material propeller are located at different valve ports of the multi-channel switching valve; and the raw material bottle of the fifth raw material propeller is used for storing the aminopolyether acetonitrile solution containing potassium carbonate.

The specific operation process is as follows:

s1, feeding the mixed solution containing F18 ions into a reaction tube by using an F18 collector.

Target water enters a corresponding valve port of the multi-channel switching valve through the target water input pipe, the multi-channel switching valve rotates the valve port to the position of the target water output pipe, and the target water flows through the QMA column through the target water output pipe and is captured by the QMA column 27; the fifth feed pusher 2 extracts aminopolyether acetonitrile solution containing potassium carbonate from the feed flask to elute F18 ions on the QMA column into the reaction tube 30. After elution, the air blowing device can be connected with the multi-channel switching valve 1 through the first control valve 15, and residual liquid of pipelines and valves is blown into the reaction tube by using blown nitrogen, so that the residual quantity is reduced.

After step S1 is completed, the control valve connected to the first recovery flask and the fifth control valve 19 are closed, and the nitrogen gas supply to the reaction tube is stopped.

S2, blowing off the reaction tube by using nitrogen, and heating the reaction tube to ensure that no liquid remains in the reaction tube;

opening a second control valve 16 between the blowing device and the reaction tube 30, quantitatively blowing nitrogen into the reaction tube through a gas flow controller, and simultaneously opening a fifth control valve 19 at the bottom of the reaction tube, a heating device 31 and a control valve connected with a first recovery bottle; heating the interior of the reaction tube to about 140 ℃ to quickly evaporate the residual liquid in the reaction tube until the reaction tube is dry and has no residue.

After step S2 ends, the blowing of nitrogen gas to the multi-channel switching valve is stopped.

S3, injecting anhydrous acetonitrile stored in a raw material bottle of the first raw material propeller 3 into the reaction tube 30 through the injection pump and the first multi-way valve 8, and then opening a control valve of the blowing device connected with the first multi-way valve to blow off residual liquid inside.

S4, synchronization step S2;

s5, injecting the mannose triflate acetonitrile solution stored in the raw material bottle of the second raw material propeller 4 into the reaction tube 30 through the injection pump and the first multi-way valve 8, and then opening the third control valve 17 of the blowing device connected with the first multi-way valve to blow off the residual liquid inside;

the nitrogen purge was then turned off and the reaction tube was heated to 30 to 103 degrees celsius for nucleophilic reaction.

S6, after the nucleophilic reaction is finished, continuously heating to 140 ℃, opening a control valve connected with the first recovery bottle 7, and removing acetonitrile in the mannose triflate acetonitrile solution.

And S7, the water for injection in the raw material bottle of the third raw material propeller 5 is pumped to the transfer bottle 33 through the injection pump, the fourth control valve 18 connected with the transfer bottle 33 through the blowing device is opened, and the water for injection in the transfer bottle is pressed out through high-pressure nitrogen and enters the reaction pipe 30 through the first three-way valve 9. And further using the high pressure generated by the nitrogen gas to make the liquid mixed with the reaction intermediate pass through another pipeline to reach the second multi-way valve 10 and the third multi-way valve 11, and to reach the first purification column 28, usually a C-18 column, and the waste liquid after passing through the first purification column 28 enters the third recovery bottle 23 through the fourth multi-way valve 12 and the second three-way valve.

And S8, repeating the step 7 to carry out first cleaning.

And S9, carrying out secondary cleaning. The injection water in the raw material bottle of the third raw material propeller 5 is injected by the injection pump and directly blown by nitrogen, reaches the first purification column 28 through the first three-way valve 9, the second multi-way valve 10 and the third multi-way valve 11, and the waste liquid after passing through the first purification column 28 enters the third recovery bottle 23 through the fourth multi-way valve 12 and the second three-way valve.

And S10, pumping the sodium hydroxide in the raw material bottle of the fourth raw material propeller 6 to the second multi-way valve 10 and the third multi-way valve 11 through an injection pump, and reaching the first purification column 28 for hydrolysis reaction to generate 18F-FDG.

And S11, pumping the injection water in the raw material bottle of the third raw material propeller 5 to the transfer bottle 33 again through the injection pump, opening a valve connected with the transfer bottle by the blowing device, and pressing the injection water in the transfer bottle out through the high-pressure nitrogen and entering the reaction tube 30 through the first three-way valve 9. And further utilizing the high pressure generated by the nitrogen to enable the liquid mixed with the reaction intermediate to reach the second multi-way valve 10 and the third multi-way valve 11 through another pipeline, taking away the 18F-FDG generated by the reaction in the liquid after the liquid passes through the first purification column 28, and finally enabling the 18F-FDG solution to enter the product bottle 26 through the fourth multi-way valve 12, the second three-way valve 13, the fifth multi-way valve 14 and the second purification column 29 through the sterile filter membrane 34.

In the above steps, each control valve, three-way valve and multi-way valve can be automatically switched and controlled by PLC according to the actual flow direction, and the unused valve port is closed. The raw material propeller and the blowing device can also be controlled by the PLC to blow air and fill raw materials at proper time.

In the embodiment shown in fig. 1, the third multi-way valve 11, the fourth multi-way valve 12, and the fifth multi-way valve 14 respectively have four outlet valves, which can connect with the four first purification columns 28 and the second purification columns 29, each of the four first purification columns can be used for preparing 18F-FDG once, the rest unused outlet valves are closed during preparation to keep the pipelines clean, after the single preparation is completed, the other one can be opened for the next 18F-FDG preparation, and the number of the corresponding channels can be increased or decreased according to actual conditions.

The foregoing is a description of preferred embodiments of the present invention, and the preferred embodiments in the preferred embodiments may be combined and combined in any combination, if not obviously contradictory or prerequisite to a certain preferred embodiment, and the specific parameters in the examples and the embodiments are only for the purpose of clearly illustrating the inventor's invention verification process and are not intended to limit the patent protection scope of the present invention, which is defined by the claims and the equivalent structural changes made by the content of the description of the present invention are also included in the protection scope of the present invention.