Card sleeve for synthesizing diagnosis and treatment integrated targeting probe and derivative thereof

Abstract

The utility model discloses a cutting sleeve for synthesizing a diagnosis and treatment integrated targeting probe and derivatives thereof, and relates to the technical field of radiopharmaceuticals, the cutting sleeve comprises a pipeline and a plurality of control valves, the pipeline comprises a sample inlet, a feed inlet, a discharge outlet, a purification port, a sample outlet and a power port; the sample injection ports comprise a first sample injection port, a second sample injection port and a third sample injection port, the first sample injection port is used for receiving nuclide molecules, and the second sample injection port and the third sample injection port are used for receiving a first reagent and a second reagent; the feed port and the discharge port are used for being connected with a reaction bottle, and the purification port is used for being connected with a purification column so as to purify a reaction product; the sample outlet is used for outputting a product; the power port is used for providing driving force, and due to the structural design, the synthesis time is shortened; the contact between operators and radioactive substances is reduced, the safety and the effectiveness of a radiopharmaceutical preparation are guaranteed, the probe preparation speed is increased, and the efficiency is improved.

Description

Technical Field

[0001] The utility model relates to the technical field of radioactive drug synthesis, and more specifically to a ferrule for synthesizing diagnosis and treatment integrated targeting probes and derivatives thereof. Background Art

[0002] PSMA (Prostate Specific Membrane Antigen, PSMA) is highly expressed in prostate cancer and is an excellent target for prostate cancer imaging. In recent years, positron-labeled PSMA has been used for PET imaging for the diagnosis of prostate cancer, such as 68 Ga-PSMA-11, DCFPyL (Pifloratadine), etc. have been used in clinical prostate cancer diagnosis research. 68 Ga-PSMA-11 has a short half-life and DCFPyL radiolabeling rate is low.

[0003] Radioactive drugs have a short shelf life due to the half-life of nuclides, and are usually prepared and used immediately. Various types of radioactive drugs are prepared on-site before being given to patients. Currently, there are two main production processes for positron isotope-labeled drugs:

[0004] One is mainly manual. The operator needs to manually remove the bombarded target from the cyclotron and then put it into the chemical synthesis module to synthesize the labeled drug. Due to safety and sterility requirements, the accelerator room, synthesis room and quality inspection room are usually isolated. The synthesis room is a sterile clean room. In the traditional operation process, the operator loads the target containing the raw materials onto the accelerator and turns on the bombardment. Then the bombarded target is taken out of the accelerator and placed in the hot cell of the synthesis room for synthesis by the chemical synthesis module. This method is susceptible to radiation damage during operation by the operator, and the operation is complicated, which is not conducive to the standardization and repeatability of the preparation process, and cannot guarantee the safety and effectiveness of radioactive drug preparations.

[0005] The other is the traditional domestic radiochemical automation equipment. This type of equipment all uses the early fixed pipeline plus solenoid valve method, which requires cleaning after each use, and there is a risk of cross-contamination between batches. At the same time, the fixed pipeline and solenoid valve method is also very easy to malfunction due to pipeline blockage and joint leakage during long-term use, resulting in marking failure.

[0006] The above information disclosed in the background technology is only used to increase the understanding of the background technology of the utility model, therefore, it may include prior art that is not known to ordinary technicians in this field. Utility Model Content

[0007] In order to solve the problems raised in the above background technology, the utility model provides a ferrule for synthesizing integrated diagnosis and treatment targeting probes and their derivatives.

[0008] The utility model provides a cartridge for synthesizing integrated diagnosis and treatment targeted probes and their derivatives, which adopts the following technical solutions:

[0009] A ferrule for synthesizing an integrated diagnosis and treatment targeted probe and its derivatives, the ferrule comprises a pipeline and a plurality of control valves, the pipeline comprises an injection port, a feed port, a discharge port, a purification port, a sample outlet port and a power port; the injection port comprises a first injection port, a second injection port and a third injection port, the first injection port is used to receive a nuclide molecule, the second injection port is used to connect a first reagent bottle to receive a first reagent in the first reagent bottle, the third injection port is used to connect a second reagent bottle to receive a second reagent in the second reagent bottle; the feed port is used to connect a reaction bottle to allow the nuclide molecule, the second reagent bottle and the third reagent bottle to be connected to the reaction bottle, so that the nuclide molecule, the second reagent bottle and the third reagent bottle can be connected to the reaction bottle, and the second ... A first reagent and a second reagent enter the reaction bottle through the feed port; the discharge port is used to connect the reaction bottle so that the substance in the reaction bottle enters the pipeline through the discharge port; the purification port includes a purification inlet and a purification outlet, and the purification inlet and the purification outlet are respectively used to connect the two ends of the purification column to purify the reaction product using the purification column; the sample outlet is used to connect the product bottle to output the product; the power port is used to connect the driving device to provide driving force to drive the reagent flow in the pipeline; multiple control valves are respectively arranged at the sample inlet, feed port, discharge port, purification port, sample outlet and power port.

[0010] In some embodiments, the pipeline further includes an enrichment port, which is disposed between the first sample inlet and the feed inlet, and includes an enrichment inlet and an enrichment outlet, which are respectively connected to both ends of the enrichment column for enriching radionuclide molecules.

[0011] In some embodiments, the control valve includes a first control valve and a second control valve, the first control valve is arranged at the enrichment inlet, and the second control valve is arranged at the enrichment outlet; the first control valve and the second control valve are three-way valves.

[0012] In some embodiments, the control valve includes a first control valve and a second control valve, the first control valve is arranged at the enrichment inlet, and the second control valve is arranged at the enrichment outlet; the first control valve and the second control valve are two-way valves.

[0013] In some embodiments, the cartridge further includes a first adsorption column and a second adsorption column; the two ends of the first adsorption column are respectively connected to the reaction bottle and the discharge port; the purification port includes a first purification port, the first purification port is arranged between the discharge port and the sample outlet, the first purification port includes a first purification inlet and a first purification outlet, the first purification inlet and the first purification outlet are respectively connected to the two ends of the second adsorption column.

[0014] In some embodiments, the purification port also includes a second purification port, which includes a second purification inlet and a second purification outlet, and the second purification inlet and the second purification outlet are respectively used to connect the two ends of the high performance liquid chromatography column, and the second purification port is arranged between the discharge port and the first purification port.

[0015] In some embodiments, the feed port includes a first feed port and a second feed port, the first feed port is disposed between the first injection port and the second injection port, and the second feed port is disposed between the second injection port and the third injection port.

[0016] In some embodiments, the power port includes a first power port and a second power port, and the first power port and the second power port are respectively located at the outermost interfaces at both ends of the pipeline; the sleeve also includes a syringe, and the syringe includes a first syringe and a second syringe, the first syringe is connected to the first power port, and the second syringe is connected to the second power port, so as to drive the flow of reagents in the pipeline by driving the syringe to provide driving force.

[0017] In some embodiments, the pipeline further includes multiple preparation ports, which are respectively arranged adjacent to the sample inlet, the sample outlet, the enrichment inlet, the feed inlet, and the purification inlet; the ferrule further includes multiple preparation bottles, which are respectively connected to the multiple preparation ports.

[0018] In some embodiments, the pipeline further includes a plurality of waste ports, which are respectively arranged adjacent to the discharge port, the enrichment outlet, and the purification outlet; the card sleeve further includes a plurality of waste bottles, which are respectively connected to the plurality of waste ports.

[0019] In some embodiments, the ferrule further comprises a base, and the base is connected to one end of the pipeline.

[0020] In some embodiments, the injection port is used to connect to an accelerator system; the nuclides include 18 F - , 131 I, 211 At, radionuclide, one or more of the nuclides used for PET imaging and for SPECT imaging, the radionuclides including alpha nuclides: 149 Tb, 153 Gd, 211 At 213 Bi, 223 Ra, 225 Ac, 230 U; β ﹣ Nuclide: 47 Sc, 64 Cu, 67 Cu, 90 Y. 152 Tb, 153 Sm, 161 Tb,177 Lu, 186 Re, 188 Re, 203 Pb, 212 Pb; radionuclides used for PET imaging include 18 F. 44 Sc, 45 Ti, 52 Mn, 52 Fe, 59 Fe, 60 Cu, 6l Cu, 62 Cu, 64 Cu, 66 Cu, 67 Cu, 66 Ga, 68 Ga, 82 Rb, 86 Y. 89 Zr, 152 Tb, 155 Gd, 157 Gd; radionuclides used for SPECT imaging include 67 Ga, 99m Tc, 111 In, 131 I. 153 Sm, 155 Tb, 165 2. 191 Pt.

[0021] In summary, the utility model includes the following beneficial technical effects:

[0022] The synthetic cassette of the present application is easy to operate, reduces the contact between operators and radioactive materials, and greatly reduces the radiation dose received by operators; reduces manual intervention, reduces manual errors, improves the standardization and repeatability of the preparation process, ensures the safety and effectiveness of radiopharmaceutical preparations, speeds up the rate of probe preparation, improves efficiency, and reduces unnecessary attenuation.

[0023] The above summary is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments and features described above, further aspects, embodiments and features of the present invention will be readily apparent by reference to the accompanying drawings and the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a schematic structural diagram of a cartridge for synthesizing an integrated diagnosis and treatment targeting probe and its derivatives in one embodiment of the utility model;

[0025] Figure 2This is a schematic diagram of the structure of a cartridge for synthesizing an integrated diagnosis and treatment targeting probe and its derivatives in Embodiment 1 of the present utility model;

[0026] Figure 3 It is a schematic diagram of the structure of a cartridge for synthesizing an integrated diagnostic and therapeutic targeted probe and its derivatives in the second embodiment of the present utility model. DETAILED DESCRIPTION

[0027] The following is combined with Figures 1 to 3 The utility model is described in further detail.

[0028] It should be noted that the drawings are schematic and not to scale. For the sake of clarity and convenience, the relative sizes and proportions of the parts shown in the drawings are exaggerated or reduced in size, and any size is only illustrative and not restrictive. In addition, the same reference symbol is used for the same structure, element or accessory appearing in more than two figures to reflect similar features.

[0029] See also Figure 1 , Figure 1 It is a schematic diagram of the structure of a ferrule for synthesizing an integrated diagnostic and therapeutic targeted probe and its derivatives in one embodiment. In this embodiment, a ferrule for synthesizing an integrated diagnostic and therapeutic targeted probe and its derivatives is provided, and the ferrule includes a pipeline 10 and a plurality of control valves. The pipeline 10 is an elongated tubular object with a connected internal channel for material flow; the pipeline 10 includes a plurality of functional interfaces, and the functional interfaces are used to connect different devices, so as to connect different devices in series through the pipeline 10 and realize the reaction of the material in the pipeline 10 system. Furthermore, a control valve is provided at each functional interface, and the control valve is used to regulate the closure of the interface. Through this arrangement, the contact between the operator and the radioactive material can be reduced, and the radiation dose received by the operator can be greatly reduced; human intervention can be reduced, human errors can be reduced, the standardization and repeatability of the preparation process can be improved, the safety and effectiveness of radiopharmaceutical preparations can be guaranteed, the rate of probe preparation can be accelerated, and efficiency can be improved.

[0030] Specifically, the pipeline 10 includes an injection port 101, a feed port 102, a discharge port 103, a purification port 104, a sample outlet 105, and a power port 106. The injection port 101 includes a first injection port 1011, a second injection port 1012, and a third injection port 1013. The first injection port 1011 is used to receive radionuclide molecules, the second injection port 1012 is used to connect to the first reagent bottle 201 to receive the first reagent in the first reagent bottle 201, and the third injection port 1013 is used to connect to the second reagent bottle 202 to receive the second reagent in the second reagent bottle 202; the feed port 102 is used to connect to the reaction bottle 30 so that the radionuclide molecules, the first reagent, and the second reagent can pass through the reaction bottle 30. The reaction bottle 30 is entered through the feed port 102; the discharge port 103 is used to connect the reaction bottle 30 so that the substance in the reaction bottle 30 enters the pipeline 10 through the discharge port 103; the purification port 104 includes a purification inlet and a purification outlet, and the purification inlet and the purification outlet are respectively used to connect the two ends of the purification column to purify the reaction product using the purification column; the sample outlet 105 is used to connect the product bottle 40 to output the product; the power port 106 is used to connect the driving device to provide driving force to drive the reagent in the pipeline 10 to flow.

[0031] The first injection port 1011 can be used to connect to the accelerator system to receive nuclide molecules. The first injection port 1011 can be a flat port or a threaded port, and can be connected to the accelerator system through a hose or a glass tube.

[0032] The second injection port 1012 and the third injection port 1012 can be flat or threaded ports for connecting to reagent bottles. Reagent bottles are used to hold precursors required for the reaction, etc. The reagent bottle can be fixedly connected to the injection port, that is, the reagent bottle is brought by the ferrule, and the reagents required for the reaction have been pre-configured, thereby reducing the contact between the operator and the reagent and improving the synthesis efficiency. It can also be an external reagent bottle so that the ferrule can be used for the synthesis of more substances. In the present application scheme, in addition to the nuclide injection port (the first injection port 1011), at least two injection ports (the second injection port 1012 and the third injection port 1012) are also provided so that the ferrule can be used for synthesis reactions performed in multiple steps, or for synthesis reactions that require step-by-step feeding.

[0033] The feed port 102 and the discharge port 103 may be flat or threaded ports, and may be connected to the reaction bottle 30 through a hose or a glass tube. The reaction bottle 30 may be a device that comes with the ferrule, that is, the ferrule is pre-assembled with the reaction bottle 30. In other embodiments, the reaction bottle 30 may also be externally connected to meet the needs of different reaction volumes.

[0034] In one embodiment, the feed port 102 includes a first feed port 1021 and a second feed port 1022, wherein the first feed port 1021 is disposed between the first injection port 1011 and the second injection port 1012, and the second feed port 1021 is disposed between the second injection port 1012 and the third injection port 1013. Generally, the raw materials from the first injection port 1011 and the second injection port 1012 enter the reaction bottle 30 through the first feed port 1021, and the raw materials from the third injection port 1013 enter the reaction bottle 30 through the second feed port 1022.

[0035] The purification port 104 generally includes a purification inlet and a purification outlet for connection with a purification column. The product is input into the purification column, purified by the purification column, and then returned to the pipeline 10 system. There can be multiple purification ports 104, that is, the product can be purified multiple times. The purification columns connected to different purification ports 104 can be different, so as to purify the product to different degrees.

[0036] The sample outlet 105 can be a flat port or a threaded port, and can be connected to the product bottle 40 through a hose or a glass tube. The product bottle 40 can be a device that comes with the ferrule, that is, the ferrule is equipped with the product bottle 40 at the sample outlet 105. In other embodiments, the product bottle 40 can also be external to meet the needs of different products. The first sample inlet 1011 and the sample outlet 105 are generally arranged at both ends of the pipeline 10, so that the raw material enters from one end of the pipeline 10, and after reaction and purification, the product is output from the other end of the pipeline 10; the cross contamination of products at different stages in the reaction process is reduced, and the synthesis efficiency and purity are improved.

[0037] The power port 106 is used to connect a driving device to provide driving force to drive the reagent in the pipeline 10 to flow. The driving device can be external, and the driving device can be a suction device, such as a syringe, a vacuum pump, etc., which can provide driving force to drive the reagent in the pipeline 10 to flow by changing the pressure in the pipeline 10 through suction.

[0038] In one embodiment, the power port 106 includes a first power port 1061 and a second power port 1062, and the first power port 1061 and the second power port 1062 are respectively located at the outermost interfaces at both ends of the pipeline 10. By arranging the two power ports 106 at both ends of the pipeline 10, a thrust can be applied at one end and a pull can be applied at the other end, so as to better control the movement of the material in the pipeline 10.

[0039] Furthermore, the synthetic ferrule also includes a syringe 50, which includes a first syringe 501 and a second syringe 502, wherein the first syringe 501 is connected to the first power port 1061, and the second syringe 502 is connected to the second power port 1062, so as to drive the flow of reagent in the pipeline 10 by providing a driving force by driving the syringe 50.

[0040] In one embodiment, the pipeline 10 further includes an enrichment port 107, which is disposed between the first sample inlet 1011 and the feed port 102, and includes an enrichment inlet 1071 and an enrichment outlet 1072, which are respectively connected to both ends of the enrichment column 60 for enriching nuclide molecules. The enrichment column 60 may be a QMA column. The QMA column is generally a short column of white plastic.

[0041] In some solutions, the first injection port 1011 can be directly connected to the accelerator system, and the nuclide molecules enter the pipeline along with the target water output by the accelerator system, for example 18 F - The target water obtained by this method has a low concentration of radionuclides, and the radionuclides need to be enriched by the enrichment column 60 to improve the reaction efficiency. In some schemes, the target water can also be pre-treated before being input into the pipeline 10, for example 131 I, 211 At, this method does not need to use an enrichment column. Therefore, some pipelines may not be provided with an enrichment port. Alternatively, an enrichment port may be designed, but whether to use an enrichment column is controlled by a control valve.

[0042] Specifically, the control valve includes a first control valve and a second control valve, the first control valve is arranged at the enrichment inlet 1071, and the second control valve is arranged at the enrichment outlet 1072; the first control valve and the second control valve are three-way valves; or the first control valve and the second control valve are two-way valves. When the control valve of the enrichment port 107 is a three-way valve, the enrichment column 60 can be controlled to be used; when the control valve of the enrichment port 107 is a two-way valve, the enrichment column 60 can be controlled not to be used.

[0043] In one embodiment, the synthesis cartridge further includes a first adsorption column 70, and both ends of the first adsorption column 70 are connected to the reaction bottle 30 and the discharge port 103, respectively. Through this connection, the material from the reaction bottle 30 first passes through the first adsorption column 70 and then enters the pipeline 10. The first adsorption column 70 can be Al 2 O 3 The column can be used to remove excess nuclide anions by adsorption to perform the first step of purification of the output material.

[0044] In one embodiment, the synthesis cartridge further includes a second adsorption column 80, the purification port 104 includes a first purification port 1041, the first purification port 1041 includes a first purification inlet 10411 and a first purification outlet 10412, the first purification inlet 10411 and the first purification outlet 10412 are respectively connected to the two ends of the second adsorption column 80, and the first purification port 104 is arranged between the discharge port 103 and the sample outlet 105. The second adsorption column 80 can be 18 C column, which can adsorb the product and then elute it to purify the product.

[0045] In one embodiment, the purification port 104 further includes a second purification port 1042, which includes a second purification inlet 10421 and a second purification outlet 10422, which are respectively used to connect the two ends of a high performance liquid chromatography column (HPLC), and the second purification port 1042 is arranged between the discharge port 103 and the first purification port 1041. With this arrangement, after the product is discharged, it is first purified by an external high performance liquid chromatography column (HPLC) before the subsequent preparation is carried out.

[0046] In one embodiment, the pipeline 10 further includes a plurality of preparation ports 108, which are respectively arranged adjacent to the sample inlet 101, the sample outlet 105, the enrichment inlet 1071, the feed inlet 102, and the purification inlet; the synthesis cartridge further includes a plurality of preparation bottles 90, which are respectively connected to the plurality of preparation ports 108. The preparation bottles 90 are used to hold the preparations required for the reaction, such as eluents, etc. Figure 1 As shown, a preparation bottle 901 is arranged near the enrichment port 107, and the preparation bottle 901 is used to hold the eluent required for eluting the enrichment column 60; a preparation bottle 902 is arranged near the feed port 102, and the preparation bottle 902 is used to hold the solvent required for eluting the reaction bottle; preparation bottles 903 and 904 are arranged near the first purification port 1041, and the preparation bottles 903 and 904 are used to hold the eluent required for eluting the second adsorption column 80; a preparation bottle 904 is arranged near the sample outlet 105, and the preparation bottle 904 is used to prepare the physiological saline required for the targeted probe preparation. The preparation bottle can be pre-configured and connected to the pipeline; it can also be external.

[0047] In one embodiment, the pipeline 10 further includes a plurality of waste ports 109, which are respectively disposed adjacent to the discharge port 103, the enrichment outlet 1072, and the purification outlet; the synthesis cartridge further includes a plurality of waste bottles, which are respectively connected to the plurality of waste ports. The waste bottles are used to receive waste liquid generated by the reaction system. The waste bottles may be pre-connected to the pipeline; or they may be externally connected.

[0048] In some embodiments, the synthetic ferrule further includes a base 100 , which is connected to one end of the pipeline 10 to provide support for the pipeline 10 .

[0049] The synthesis cartridge provided in the above embodiments can be applied to the synthesis of various radionuclide markers. 18 F - , 131 I, 211At, a radionuclide, a nuclide used for PET imaging, one or more of a nuclide used for SPECT imaging, wherein the radionuclide includes an alpha nuclide: 149 Tb, 153 Gd, 211 At 213 Bi, 223 Ra, 225 Ac, 230 U; β ﹣ Nuclide: 47 Sc, 64 Cu, 67 Cu, 90 Y. 152 Tb, 153 Sm, 161 Tb, 177 Lu, 186 Re, 188 Re, 203 Pb, 212 Pb; the nuclides used for PET imaging include 18 F. 44 Sc, 45 Ti, 52 Mn, 52 Fe, 59 Fe, 60 Cu, 6l Cu, 62 Cu, 64 Cu, 66 Cu, 67 Cu, 66 Ga, 68 Ga, 82 Rb, 86 Y. 89 Zr, 152 Tb, 155 Gd, 157 Gd; the nuclides used for SPECT imaging include 67 Ga, 99m Tc, 111 In, 131 I. 153 Sm, 155 Tb, 165 2. 191Pt. It is also suitable for the synthesis of a variety of targeted probes and their derivatives. For example, it can not only be used for the synthesis of TCO-Tz-PSMA, but also support the synthesis and production of probe derivatives in the future. The radionuclide-labeled targeted probe synthesis cartridge provided in the above implementation mode is produced by a cyclotron, transmitted to a radiolabeling hot chamber through a dedicated pipeline, and finally synthesized by a multifunctional automatic chemical synthesis module. The final product shortens the synthesis time and is easy to operate with full automation; it reduces the contact between operators and radioactive substances, greatly reducing the radiation dose received by operators; it avoids manual intervention, reduces manual errors, improves the standardization and repeatability of the preparation process, ensures the safety and effectiveness of radiopharmaceutical preparations, speeds up the rate of probe preparation, improves efficiency, and reduces unnecessary attenuation. The entire cartridge is modularly designed and can be used as a disposable cartridge.

[0050] Embodiment 1

[0051] The first embodiment of the utility model discloses a ferrule for synthesizing an integrated diagnosis and treatment targeting probe and its derivatives. Figure 2 , Figure 2 Schematic diagram of the structure of the ferrule used for synthesizing the integrated diagnosis and treatment targeted probe and its derivatives in the first embodiment of the utility model. In this embodiment, the synthetic ferrule can be used as a disposable ferrule for synthesizing the probe. 18 F-TTCO-PSMA.

[0052] like Figure 2 As shown, the synthetic ferrule includes a pipeline 10, on which 24 functional interfaces are arranged, and each functional interface is provided with a control valve, specifically, a V1 three-way valve, a V2 three-way valve, a V3 three-way valve, a V4 three-way valve, a V5 three-way valve, a V6 three-way valve, a V7 three-way valve, a V8 three-way valve, a V9 three-way valve, a V10 three-way valve, a V11 three-way valve, a V12 three-way valve, a V13 three-way valve, a V14 three-way valve, a V15 three-way valve, a V16 three-way valve, a V17 three-way valve, a V18 three-way valve, a V19 three-way valve, a V20 three-way valve, a V21 three-way valve, a V22 three-way valve, a V23 three-way valve, and a V24 three-way valve; by adjusting each control valve, the flow direction of the material in the synthetic ferrule can be regulated.

[0053] Among them, the functional interfaces at the V1 three-way valve and the V24 three-way valve are the first power port and the second power port respectively, and the first power port and the second power port are respectively connected to syringes to push the syringes to form driving force.

[0054] The functional interfaces at the V2 three-way valve and the V9 three-way valve are the first injection port and the second injection port, respectively; when installed, the first injection port is connected to the accelerator system to receive radionuclide molecules, and the second injection port is connected to the first reagent bottle, which contains the precursors required for the reaction. The functional interface at the V7 three-way valve is the first feed port; when installed, the first feed port is connected to the reaction bottle. The functional interfaces at the V4 three-way valve and the V5 three-way valve are the enrichment inlet and the enrichment outlet, respectively; when installed, the enrichment inlet and the enrichment outlet are connected to the two ends of the QMA column, respectively. The functional interfaces at the V3 three-way valve and the V8 three-way valve are the preparation port; when installed, the preparation port is connected to the preparation bottle, which contains the eluent required for the reaction. The functional interface at the V6 three-way valve is the waste port; when installed, the waste port is connected to the waste bottle to receive the waste liquid generated by the system.

[0055] The synthetic reaction operation is as follows:

[0056] Open the three-way valves V2, V4, V5 and V6 to make the accelerator 18 F - The target water flows through the QMA column, 18 F - The target material is attached to the QMA column and is recycled into waste bottle 1. Close the three-way valves V2 and V6; open the three-way valves V1, V3, and V7, and push the syringe to load the eluent 1 (proportion of K2.2.2, K 2 CO 3 , ACN aqueous solution) flows through the QMA column, and the eluent after washing carries 18 F - Enter the reaction bottle. Close the V3-V5 three-way valves; open the V24 three-way valve, heat the reaction bottle to 80-120°C (preferably 95°C), and evaporate the eluent in the reaction bottle under reduced pressure; in this process, an inert gas can also be supplied through the first power port to evaporate the eluent in the reaction bottle under inert gas purging and negative pressure conditions. Open the V8 three-way valve, add acetonitrile to the reaction bottle, and then evaporate it again; close the V8 three-way valve. Open the V9 three-way valve; add the precursor solution to the reaction bottle, then seal the reaction bottle, and heat it to 80-150°C (preferably 120°C), and fluorination reaction for 10-20 minutes; after the fluorination reaction is completed, cool the first reaction bottle to room temperature -80°C (preferably 60°C).

[0057] The functional interface at the V11 three-way valve is the third sample inlet; when installed, the third sample inlet is connected to the second reagent bottle, which contains the deprotection agent TFA. The functional interface at the V10 three-way valve is the second feed inlet; when installed, the second feed inlet is connected to the reaction bottle. The functional interface at the V12 three-way valve is the discharge port; when installed, the discharge port is connected to the reaction bottle.

[0058] In this embodiment, for synthesizing 18 There are multiple active sites in the precursor of F-TTCO-PSMA, and some of the active sites need to be protected, so there are protecting groups; the protecting groups need to be removed after the reaction. Open the V10 three-way valve and the V11 three-way valve, add the deprotecting agent to the reaction bottle, and carry out the deprotection reaction. After the reaction, close the V10 three-way valve and the V11 three-way valve, open the V1 three-way valve and the V12 three-way valve, and press the substances in the reaction bottle into the pipeline.

[0059] The functional interface at the three-way valve V14 and V15 is the first purification port. When installed, the inlet and outlet of the first purification port are connected to the external HPLC system respectively; the functional interface at the three-way valve V19 and V20 is the second purification port. When installed, the inlet and outlet of the second purification port are connected to the C 18 The two ends of the column are connected. The functional interface at the V17 three-way valve and the V18 three-way valve is the preparation port; when installed, the preparation port is connected to the preparation bottle, and the preparation bottle contains the required eluent. The functional interface at the V21 three-way valve is the waste port; when installed, the waste port is connected to the waste bottle to receive the waste liquid generated by the system.

[0060] Open the three-way valves V14 and V15 to allow the product to flow through the HPLC system and return to pipeline 10 after one purification; open the three-way valves V19, V20, and V21, and then pass through C 18 Column, product adsorbed on C 18 On the column, open the V17 three-way valve to elute the product.

[0061] The functional interface at the V23 three-way valve is the sample outlet. When installed, the sample outlet is connected to the product bottle. The functional interface at the V22 three-way valve is the preparation port. When installed, the preparation port is connected to the preparation bottle, which contains physiological saline for preparing the targeted probe preparation.

[0062] Open the three-way valve V22 and the three-way valve V23, and the purified product is mixed with physiological saline and then enters the product bottle to obtain a targeted probe preparation.

[0063] Embodiment 2

[0064] The first embodiment of the utility model discloses a ferrule for synthesizing an integrated diagnosis and treatment targeting probe and its derivatives. Figure 3 , Figure 3 This is a schematic diagram of the structure of the ferrule used for synthesizing the integrated diagnosis and treatment targeted probe and its derivatives in Example 1 of the utility model. In this embodiment, the synthesis ferrule may not be provided with an enrichment interface and an enrichment center, and can be applied to nuclide molecules that do not require enrichment treatment. The working principle of the ferrule in this embodiment, except for the step of enriching nuclide molecules, the other steps are the same as those in Example 1. Please refer to the above description for details, and no further description will be given here.

[0065] The standard parts used in the utility model can all be purchased from the market, and special-shaped parts can be customized according to the instructions and the drawings. The specific connection methods of each part adopt the conventional means such as mature bolts, rivets, welding, etc. in the existing technology. The machinery, parts and equipment all adopt the conventional models in the existing technology, and the circuit connection adopts the conventional connection method in the existing technology, which will not be described in detail here.

[0066] In the description of the present utility model, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. The meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0067] In the present invention, unless otherwise clearly specified and limited, the terms "install", "connect", "connect", "fix" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0068] In the present utility model, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, a first feature being "above", "above" or "above" a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being "below", "below" or "below" a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0069] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example" or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the utility model. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, unless they are contradictory.

[0070] In the drawings of the embodiments disclosed in the present utility model, only the structures related to the embodiments disclosed in the present utility model are involved, and other structures can refer to the general design. In the absence of conflict, the same embodiment and different embodiments of the present utility model can be combined with each other.

[0071] Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art may still modify the technical solutions described in the aforementioned embodiments, or make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.

Claims

1. A cartridge for synthesizing an integrated diagnostic and therapeutic targeting probe and its derivatives, characterized in that: The ferrule includes a pipeline and a plurality of control valves, wherein the pipeline includes: The injection port comprises a first injection port, a second injection port and a third injection port, wherein the first injection port is used to receive nuclide molecules, the second injection port is used to connect to a first reagent bottle to receive a first reagent in the first reagent bottle, and the third injection port is used to connect to a second reagent bottle to receive a second reagent in the second reagent bottle; A feed port, used to connect the reaction bottle, so that the nuclide molecule, the first reagent, and the second reagent enter the reaction bottle through the feed port; A discharge port, used to connect the reaction bottle, so that the material in the reaction bottle enters the pipeline through the discharge port; A purification port, comprising a purification inlet and a purification outlet, wherein the purification inlet and the purification outlet are respectively used to connect two ends of a purification column to purify the reaction product using the purification column; The sample outlet is used to connect the product bottle to output the product; A power port, used to connect a driving device to provide driving force to drive the reagent in the pipeline to flow; The multiple control valves are respectively arranged on the sample inlet, feed inlet, discharge port, purification port, sample outlet and power port.

2. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to claim 1, characterized in that: The pipeline also includes: The enrichment port is arranged between the first sample inlet and the feed inlet, and comprises an enrichment inlet and an enrichment outlet, wherein the enrichment inlet and the enrichment outlet are respectively connected to two ends of the enrichment column and are used for enriching the nuclide molecules.

3. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to claim 2, characterized in that: The control valve comprises a first control valve and a second control valve, the first control valve is arranged at the enrichment inlet, and the second control valve is arranged at the enrichment outlet; The first control valve and the second control valve are three-way valves; or The first control valve and the second control valve are two-way valves.

4. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to any one of claims 1 to 3, characterized in that: The cartridge also includes a first adsorption column and a second adsorption column, and the two ends of the first adsorption column are respectively connected to the reaction bottle and the discharge port; the purification port includes a first purification port, and the first purification port includes a first purification inlet and a first purification outlet, and the first purification inlet and the first purification outlet are respectively connected to the two ends of the second adsorption column, and the first purification port is arranged between the discharge port and the sample outlet.

5. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to claim 4, characterized in that: The purification port also includes a second purification port, which includes a second purification inlet and a second purification outlet, and the second purification inlet and the second purification outlet are respectively used to connect to the two ends of the high-performance liquid chromatography column, and the second purification port is arranged between the discharge port and the first purification port.

6. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to any one of claims 1 to 3, characterized in that: The feed port includes a first feed port and a second feed port, the first feed port is arranged between the first injection port and the second injection port, and the second feed port is arranged between the second injection port and the third injection port.

7. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to any one of claims 1 to 3, characterized in that: The power port includes a first power port and a second power port, wherein the first power port and the second power port are respectively located at the outermost interfaces at both ends of the pipeline; The card sleeve also includes a syringe, and the syringe includes a first syringe and a second syringe, the first syringe is connected to the first power port, and the second syringe is connected to the second power port, so as to drive the reagent in the pipeline to flow by driving the syringe to provide a driving force.

8. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to any one of claims 1 to 3, characterized in that: The pipeline further comprises a plurality of preparation ports, which are respectively arranged adjacent to the sample inlet, the sample outlet, the enrichment inlet, the feed inlet, and the purification inlet; the cartridge further comprises a plurality of preparation bottles, which are respectively connected to the plurality of preparation ports; The pipeline also includes a plurality of waste ports, which are respectively arranged adjacent to the discharge port, the enrichment outlet, and the purification outlet; the ferrule also includes a plurality of waste bottles, which are respectively connected to the plurality of waste ports.

9. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to any one of claims 1 to 3, characterized in that: The ferrule also includes a base, which is connected to one end of the pipeline.

10. The ferrule for synthesizing the integrated diagnosis and treatment targeting probe and its derivatives according to any one of claims 1 to 3, characterized in that: The first injection port is used to connect to the accelerator system; the nuclide molecule includes 18 F - , 131 I, 211 At, a radionuclide, a nuclide used for PET imaging, one or more of a nuclide used for SPECT imaging, wherein the radionuclide includes an alpha nuclide: 149 Tb, 153 Gd, 211 At 213 Bi, 223 Ra, 225 Ac, 230 U; β ﹣ Nuclide: 47 Sc, 64 Cu, 67 Cu, 90 Y. 152 Tb, 153 Sm, 161 Tb, 177 Lu, 186 Re, 188 Re, 203 Pb, 212 Pb; the nuclides used for PET imaging include 18 F. 44 Sc, 45 Ti, 52 Mn, 52 Fe, 59 Fe, 60 Cu, 6l Cu, 62 Cu, 64 Cu, 66 Cu, 67 Cu, 66 Ga, 68 Ga, 82 Rb, 86 Y. 89 Zr, 152 Tb, 155 Gd, 157 Gd; the nuclides used for SPECT imaging include 67 Ga, 99m Tc, 111 In, 131 I. 153 Sm, 155 Tb, 165 2. 191 Pt.

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