An automated system for 68Ge separation and purification

Abstract

The utility model discloses a kind of 68 Automatic system of Ge separation and purification.The separation and purification system includes: control unit, including industrial computer, programmable logic controller PLC and control software, for sending control instruction and receiving monitoring signal;Execution unit, including at least one multi-channel switching valve, at least one peristaltic pump and at least one liquid level monitor, controlled by control unit;Separation unit, including at least two sets of series separation column system consisting of actinium resin column and glucose gel column, and separation column system is accessed pipeline in parallel connection mode;Pipeline unit, including hard tube, hose and joint connected each unit.The utility model series-parallel connection column system design makes a set of column when working, another set can simultaneously regenerate or replace, realizes the continuous production mode of "non-stop", greatly improves 68 The production efficiency of Ge, lays the foundation for large-scale application.

Description

Technical Field

[0001] This utility model relates to a 68 The automated system for Ge separation and purification belongs to the field of positron emission tomography (PET) technology. Background Technology

[0002] 68 Ga, with a half-life of 67.71 min, is one of the commonly used nuclides in clinical PET imaging for nuclear medicine. Currently, 68 Ga-DOTATATE, 68 Several radiopharmaceuticals, including Ga-PSMA, have been approved for use in the diagnosis of various types of tumors, including neuroendocrine tumors and prostate cancer. More importantly, compared to... 18 F-FDG, 68 Ga-FAPI exhibits higher detection rates, sensitivity, and accuracy for pancreatic cancer, esophageal cancer, and non-small cell lung cancer. Numerous novel Ga-FAPI formulations are being developed in domestic nuclear medicine clinical practice. 68 Ga2-targeted broad-spectrum tumor imaging agents are used for PET / CT diagnosis of more than 20 types of tumors, including gastric cancer and breast cancer. Therefore, it can be seen that... 68 Ga has been widely used in clinical practice, benefiting cancer patients.

[0003] 68 The development of Ga drugs is based on the preparation and separation of radionuclides. Typically, this is achieved through rinsing... 68 Ge / 68 Ga generator obtains 68 Ga. Currently, the domestic market 68 Ge / 68 While Ga generators have achieved partial domestic industrialization, most are still assembled domestically using imported advanced technology. To achieve... 68 Ge / 68 The most fundamental and crucial aspect of achieving complete autonomy in Ga generators is realizing... 68 High-efficiency preparation and separation of Ge. Currently, domestic and international efforts are focused on... 68 The production and separation processes for Ge mainly involve solvent extraction, fractionation, and chromatography. Compared to the other two methods, chromatography can achieve... 68 The automated and continuous separation of Ge can minimize the need for [other processes]. 68 Ge loss. Previously, we conducted a dual-column process using a Chelex 100 column coupled with glucose gel resin to extract Ge from an irradiated Ga-Ni alloy target. 68 Ge was separated and milli-cubic-level high purity was successfully obtained. 68However, experiments revealed that when the Ga-Ni alloy target was plated on a copper substrate, the dissolution process involved the use of large amounts of high-concentration acid and hydrogen peroxide, resulting in the dissolution of a significant amount of Cu. Subsequently, a large amount of high-concentration alkali was used to adjust the pH of the loading solution. To ensure the complete dissolution of the large amount of Cu, the volume of the loading solution increased dramatically, leading to a sharp rise in subsequent waste liquid. Therefore, developing novel color layering processes is crucial to reducing waste liquid volume and simplifying the entire operation. Utility Model Content

[0004] The purpose of this utility model is to provide a 68 An automated system for the separation and purification of Ge, solving the problem of separating Ge from an irradiated Ga-Ni alloy target. 68 Ge has problems such as large waste liquid generation, complex and cumbersome operation process, low degree of automation, and difficulty in achieving continuous large-scale production.

[0005] The present invention provides a means for achieving 68 Continuous-automated separation and purification of Ge 68 Ge separation and purification system, including: The control unit, including an industrial computer, a programmable logic controller (PLC), and control software, is used to send control commands and receive monitoring signals. The execution unit includes at least one multi-channel switching valve, at least one peristaltic pump, and at least one liquid level monitor, and is controlled by the control unit; The separation unit includes at least two series separation column systems consisting of actinide columns and glucose gel columns, wherein the separation column systems are connected to the pipeline in parallel. Piping units, including rigid pipes, flexible pipes and fittings connecting the various units; The control unit controls the channel switching of the multi-channel switching valve and the start / stop and flow rate of the peristaltic pump to achieve automatic switching, delivery and alternating work-regeneration cycles of the solution between parallel separation column systems.

[0006] Preferably, the multi-channel switching valve includes at least two eight-channel switching valves and at least four three-channel switching valves, and the flow path can be switched between flowing through the separation column system and direct connection mode through the programming control of the control unit.

[0007] The control unit also includes a database for storing system operating parameters, equipment status information, and event logs in a time-series manner to ensure the traceability of operating data.

[0008] Using the aforementioned automated system 68 Ge separation and purification can be carried out according to the following steps: S1. Adjust the acidity of the Ga-Ni alloy target solution to 2.0-5.0 mol / L; S2. The solution is passed into a first separation column packed with actinide for adsorption, and the first separation column is washed with a first eluent to remove impurities. S3. Elute the adsorbate on the first separation column using the first eluent. 68 Ge, obtained containing 68 Ge's eluent; S4, the contents of 68 The eluent of Ge is passed into a second separation column packed with glucose gel resin for adsorption. S5. Elute the second separation column with the second eluent to remove impurities; S6. Desorb the adsorbed material on the second separation column using the second eluent. 68 Ge, which is purified 68 Ge products.

[0009] In step S1, the Ga-Ni alloy target is dissolved using a dissolving device to obtain the solution; The dissolving apparatus includes: The melting tank has an internal support structure for placing the Ga-Ni alloy target, so that the target surface and the bottom of the tank are separated. A dissolving cap is provided on the dissolving tank and has at least one vent hole for safely releasing the gas generated during the dissolving process. The clamp is slidably connected to the melting tank and is used to press and fix the Ga-Ni alloy target.

[0010] Preferably, the upper edge of the dissolving tank is provided with a slide rail, and the clamp is slidably mounted on the dissolving tank via the slide rail.

[0011] Preferably, the bottom of the clamp is a frame-type support structure, forming a hollow area. The hollow area is trapezoidal in shape around its perimeter for stable placement and quick assembly / disassembly of the Ga-Ni alloy target. Preferably, the entire material of the dissolving device is polytetrafluoroethylene.

[0012] In step S2, the first eluent is an acid with a concentration of 2.0-5.0 mol / L; In step S3, the first eluent is a sodium citrate solution with a pH of 10.0-13.0 and a concentration of 0.6-1.2 mol / L.

[0013] In step S5, the second rinsing solution sequentially includes: a sodium citrate solution with a concentration of 0.001-1.5 mol / L, an alkaline solution with a pH of 10.0-13.0, and deionized water; In step S6, the second eluent is a hydrochloric acid solution with a concentration of 0.1-2.0 mol / L.

[0014] In the above method, adsorption, elution, and desorption / elution are achieved on the first separation column. The treated sample solution (loading solution) is passed through the actinide resin column by adsorption, so that... 68 Ge is selectively adsorbed onto the resin; unadsorbed or weakly adsorbed impurity ions are removed by rinsing; the target nuclide is then desorbed / eluted. 68 Ge is desorbed from the resin and collected as the desired product.

[0015] This utility model is a continuous-automatic 68 The Ge separation and purification system solves the following technical problems: This invention addresses the drawbacks of manual operation: traditional manual separation processes are cumbersome, time-consuming, and lack repeatability, and personnel are exposed to a radioactive environment. The new system achieves full automation, eliminates human error, and ensures operator safety.

[0016] Achieving continuous production: 68 Ge has a long half-life (270 days), making it suitable for mass production. In manual processes, column regeneration is too time-consuming, becoming a production bottleneck. This system breaks through this bottleneck by using a parallel design of two column systems, achieving a "hot switching" mode where one system is working while the other is regenerating or on standby.

[0017] Improved product consistency and reliability: The system precisely controls the flow rate, volume, and flow path through programming, ensuring high repeatability and high purity of each batch of products, meeting the quality requirements of medical-grade raw materials.

[0018] Reduced reagent consumption and waste liquid generation: The system avoids the problem of excessive reagent use common in manual operation through precise liquid delivery and switching, thus reducing the amount of waste liquid at the source from an engineering perspective.

[0019] Compared with the prior art, the significant technical effects brought about by this utility model are as follows: High degree of automation and safe and easy operation: The fully automatic separation system realizes the full-process automated control from rinsing, sample loading, elution to column regeneration, reducing manual operation, reducing the risk of personnel exposure to radiation, and improving the reproducibility and reliability of the process.

[0020] Enables continuous production: The unique series-parallel column system design allows one set of columns to be regenerated or replaced simultaneously while another set is in operation, achieving a "non-stop" continuous production mode and greatly improving efficiency. 68 Ge's production efficiency has laid the foundation for large-scale application.

[0021] High system integration and stable operation: The system adopts a modular design and has complete monitoring, data logging and fault diagnosis functions, ensuring long-term operational stability and product quality traceability. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the Ga-Ni alloy target dissolution device used in this embodiment of the invention.

[0023] Figure 2 This is provided in the embodiments of the present utility model. 68 Flowchart of the Ge separation method.

[0024] Figure 3 yes 68 γ-ray spectra before and after Ge separation.

[0025] Figure 4 This utility model provides 68 Schematic diagram of the Ge continuous-automatic separation system.

[0026] Figure 5 This utility model provides 68 Electrical schematic diagram of Ga continuous-automatic separation system. Detailed Implementation

[0027] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0028] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0029] In order to overcome the existing 68 Ge separation technology suffers from technical bottlenecks such as large wastewater generation, complex and cumbersome operation processes, low automation levels, and difficulty in achieving continuous large-scale production. This paper presents a novel solution integrating specialized equipment, efficient processes, and automated systems to achieve [the desired results]. 68 The automated preparation of Ge with high recovery rate, high purity, and low waste liquid provides... 68 Ge / 68 This provides core material support for the complete localization and commercial application of Ga generators.

[0030] The continuous-automatic separation system provided by this utility model is an automated system consisting of a control unit, an execution unit, a separation unit, and a pipeline unit. It innovatively adopts a parallel design of two separation column systems, and through program-controlled multi-channel switching valves and peristaltic pumps, it realizes online thermal switching and alternating "work-regeneration" cycles of the separation columns, thereby achieving full automation of the process and continuity of production.

[0031] use Figure 1 The apparatus shown is for dissolving Ga-Ni alloys and mainly includes a dissolving tank, a dissolving tank cover, and clamps.

[0032] like Figure 1 As shown, the dissolution tank features a stepped configuration, symmetrically distributed on both sides of the Ga-Ni alloy target. A 5-8mm gap is reserved between the target surface and the bottom of the tank. This design ensures sufficient reaction space for the Ga-Ni alloy during dissolution, effectively improving dissolution efficiency. A sliding rail device is provided along the upper edge of the tank, allowing for flexible adjustment of the clamp position; the outer edge of the tank serves as a dedicated load-bearing area for the dissolution tank cover, facilitating sealing operations.

[0033] like Figure 1 As shown, the top of the dissolving tank cover has a double-hole structure. During the dissolving and heating process, this design can provide an exhaust channel for the generated gas, ensuring the safety and stability of the reaction process and preventing the pressure from rising due to gas accumulation, which would affect the normal progress of the dissolving reaction.

[0034] like Figure 1 As shown, the clamp body is a rectangular block with a screw through-hole at the top, allowing for secure fixing of the Ga-Ni alloy target via screw tightening. Its bottom employs a frame-type support structure, forming a hollow area with a trapezoidal design around its perimeter. This structure enhances the clamp's support strength, ensuring reliability when fixing the alloy target; furthermore, the trapezoidal design facilitates the installation and removal of the Ga-Ni alloy target, effectively improving operational convenience and work efficiency.

[0035] Example 1, used for 68 Ge's Continuous-Automatic Separation System like Figure 4 As shown, the present invention provides a method for... 68 Ge's continuous-automatic separation system mainly includes a control unit, an execution unit, a separation unit, and a piping unit.

[0036] The control unit includes an industrial computer, user interface, database, switch, serial port server, A / D conversion module, etc.; the execution unit includes at least two eight-channel switching valves, one peristaltic pump, one liquid level sensor and four three-channel switching valves; the separation unit includes at least two sets of series-parallel separation column systems; the piping unit includes at least switching valve connectors, rigid pipes, flexible pipes, Luer connectors, liquid storage bottles, liquid receiving bottles, etc.

[0037] The connection methods for continuous-automation systems are as follows: The storage bottle A1-8 is connected to each channel of the input terminal of the switching valve VA. The output terminal VA0 of the switching valve VA is connected to the solution inlet of the peristaltic pump PU hose. The solution outlet of the peristaltic pump PU hose is connected to the input terminal VB0 of the switching valve VB. The level sensor LM is placed between the peristaltic pump PU and the switching valve VB.

[0038] The connection methods of the switching valves VB, VC, VD and VE are divided into flow through the separation column system (there are two main separation column systems, namely separation column system one consisting of GA column and GB column and separation column system two consisting of GC column and GD column). The connection method for the flow through the separation column system is as follows: the output port VB1 (or VB2) of the switching valve VB is connected to the inlet of the GA column (or GC column); the outlet of the GA column (or GC column) is connected to the input port VC1 (or VC2) of the switching valve VC; the output port VC0 of the switching valve VC is connected to the input port VD0 of the switching valve VD; the output port VD1 (or VD2) of the switching valve VD is connected to the inlet of the GB column (or GD column); and the outlet of the GB column (or GD column) is connected to the input port VE1 (or VE2) of the switching valve VE. Alternatively, the direct connection method is as follows: the output port VB3 of the switching valve VB is connected to the input port VC3 of the switching valve VC; the output port VC0 of the switching valve VC is connected to the input port VD0 of the switching valve VD; and the output port VD3 of the switching valve VD is connected to the input port VE3 of the switching valve VE.

[0039] The output port VE0 of the switching valve VE is connected to the input port VF0 of the switching valve VF, and each outlet of the output port VF of the switching valve is connected to the receiving bottle B1-8.

[0040] All of the above is controlled by the control unit. By inputting commands, the switching valve is rotated to the preset channel, the peristaltic pump (PU) extracts and delivers the liquid, and the liquid level sensor monitors the liquid flow status.

[0041] Switching valves VA and VF are preferably eight-channel switching valves. Switching valves VB, VC, VD, and VE are preferably three-channel switching valves.

[0042] Storage bottles A1-8 are preferably used to hold Ga-Ni target solution, sulfuric acid with a concentration of 3.0-5.0 mol / L, sodium citrate solution with a concentration of 0.9-1.2 mol / L (pH 10.0-13.0), sodium citrate solution with a concentration of less than 0.1 mol / L (pH 10.0-13.0), alkaline solution with a pH of 10.0-13.0, deionized water, and hydrochloric acid with a concentration of 0.01-0.1 mol / L. A8 is used as a spare storage bottle.

[0043] Receiving bottle B1 is preferably used to hold radioactive waste liquid after separation by GA (or GC) column; B2 is preferably used to hold radioactive waste liquid after separation by GB (or GD) column; B3 is preferably used to hold non-radioactive waste liquid; and B4 is preferably used to hold... 68 Ge product. B5-8 is used as a spare receiving bottle.

[0044] Device connection relationships are as follows Figure 5 As shown, the multi-channel switching valve, liquid level sensor, and peristaltic pump P1 are connected in series by the liquid pipeline. The switching valve, peristaltic pump P1, syringe pump P2, liquid level sensor, and pH monitor are connected to the PLC communication module through a communication cable. By configuration, the state of the PLC's internal output register is established to correspond one-to-one with the state of each actuator. The PLC establishes communication with the host computer through the standard TCP / IP protocol, and the communication process is controlled by the host computer software.

[0045] The specific operation process is as follows: Initially, with no command input, the multi-channel switching valve is in automatic reset mode, and P1 and P2 are in stop mode. Input a command to the host computer to move VA to VA8, VB to VB1, VC to VC1, and VD to VD4, thus opening the liquid pipeline from left to right. Input a command to open P1, purging air from the pipeline.

[0046] Will 68 The Ge separation and purification steps are input into the control program and execution begins: Step 1: Activate column C1. Input the command to make the liquid pipeline open according to VA2-VB5-VC5-VD4. Turn on P1 and keep it open for a period of time to activate column G1. Connect the tail liquid to B4. Step 2, activate column C2. Input the command to first connect the liquid line according to VA4-VB6-VC6-VD4, turn on P and keep it for a period of time, then connect the liquid line according to VA5-VB6-VC6-VD4, and connect the tail liquid to B4. Step 3, C1 column purification 68 Ge, input the command to connect the liquid pipeline in the order VA1-VB5-VC5-VD1, turn on P and hold for a period of time, then connect the liquid pipeline in the order VA2-VB5-VC5-VD1 to perform the sample loading operation, and connect the tail liquid to B1. Then connect the liquid pipeline in the order VA3-VB5-VC5-VD3 to perform the rinsing operation, and connect the tail liquid to B3. Step 4, pH adjustment: Enter the command to turn on P2 and adjust the pH value; Step 5, C2 column purification 68Ge, input the following commands: First, connect the liquid line as VA5-VB6-VC6-VD3, turn on P and hold for a period of time, then connect the tail liquid to B3. Next, connect the liquid line as VA10-VB6-VC6-VD4 to perform the sample loading operation, then connect the tail liquid to B4. Then, connect the liquid line as VA5-VB6-VC6-VD4 to perform the rinsing operation, then connect the tail liquid to B4; connect the liquid line as VA6-VB6-VC6-VD4 to perform the rinsing operation, then connect the tail liquid to B4; connect the liquid line as VA7-VB6-VC6-VD4 to perform the rinsing operation, then connect the tail liquid to B4; connect the liquid line as VA8-VB6-VC6-VD4 to perform the rinsing operation, then connect the tail liquid to B4; finally, connect the liquid line as VA9-VB6-VC6-VD2 to perform the rinsing operation and desorption. 68 Ge, the tail liquid is connected to B2; After the above steps are completed, bottles B2, B3, and B4 contain the product. 68 Ge products, radioactive waste liquids and non-radioactive waste liquids.

[0047] The redundant channels, pipelines, and empty bottles of the switching valve are used as backups to ensure the stability of the entire automated separation system.

[0048] Example 2 This utility model 68 The electrical schematic diagram of the Ga continuous-automatic separation system is shown below. Figure 5 As shown.

[0049] The system uses an industrial computer as the core control unit. The industrial computer communicates with the switch via IP protocol, and the user interface sends operation commands to the industrial computer via HMI protocol. A serial server receives commands from the industrial computer and controls the peristaltic pump and switching valve via RS485 to achieve quantitative control and precise adjustment of the liquid. Simultaneously, it acquires 4-20 mA analog signals from the level sensor received by the A / D conversion module to monitor the liquid status in the pipeline in real time. All actuators and sensors communicate with the host computer via the serial server and switch through the Modbus RTU protocol.

[0050] Operators can use the user interface to visually view the operating status of the entire separation system, including key information such as the peristaltic pump speed, the opening and closing status of the switching valve, and real-time data from the liquid level sensor. Simultaneously, operators can also use this interface to input commands or pre-set process scripts into the industrial control computer, achieving automated control and ensuring the system's precise, efficient, and stable operation.

[0051] The database stores key information about the system's operation using SQL, including basic parameters such as peristaltic pump flow setpoints and switching valve status records, as well as equipment status information such as pump speed, real-time liquid level, pressure, and temperature transmitted via the Modbus RTU network, and saves them in time series. It also records event logs such as operation command execution status and abnormal alarms, supports multi-dimensional data query and analysis, provides a basis for fault diagnosis, and ensures the integrity and traceability of operational data.

[0052] Example 3 68 Isolation and purification of Ge The Ga-Ni alloy target was dissolved in a Ga-Ni dissolution apparatus using a mixture of concentrated sulfuric acid and hydrogen peroxide, and the dissolution time was 3.0 h.

[0053] The continuous-automatic separation system of this utility model is used for 68 The process for separating and purifying Ge is as follows: Figure 2 As shown, the target solution was diluted with deionized water to an acidity of 4.0 mol / L. After being passed through the activated separation column one, the column one was washed with 33.0 mL of sulfuric acid with an acidity of 4.0 mol / L. The radioactive waste liquid was collected, and a large number of impurity nuclides and target matrix elements were removed. 68 Ge was adsorbed onto the first separation column. It was then eluted with a 1.0 mol / L sodium citrate solution at pH 12.5. 68 The eluent was directly fed into the activated separation column 2. After eluent was used, the column was rinsed successively with sodium citrate solution (pH 12.5, concentration 1.0 mol / L), sodium citrate solution (pH 12.5, concentration 0.001 mol / L), alkaline solution (pH 12.5), and deionized water. Finally, the column was desorbed using a 0.1 mol / L hydrochloric acid solution. 68 Ge was finally obtained, with a volume of 8.0 mL. 68 Ge product. —This is a specific embodiment; please change each parameter to a specific value! In this embodiment, the preferred resin for separation column one is actinide resin, and the preferred resin for separation column two is glucose gel resin G25.

[0054] 68 Ge recovery rate can reach about 90%.

[0055] The γ spectra before and after separation in this embodiment are as follows: Figure 3 As shown, after separation by actinide column chromatography, a large number of impurity nuclides are removed, and only [the remaining nuclides are visible]. 65 The gamma-ray spectra peaks of Zn impurity nuclides were observed. After further separation by glucose gel column chromatography, only [the gamma-ray peaks were observed]. 68 Ga / 68 Ge (68 Ge is a beta nuclide and does not emit gamma rays, therefore the test sample awaits the daughter nuclide. 68 The gamma spectrum peak was measured after Ga was balanced with the parent nuclide.

Claims

1. A continuous-automation 68 Ge separation and purification system, characterized in that include: The control unit, including an industrial computer, a programmable logic controller (PLC), and control software, is used to send control commands and receive monitoring signals. The execution unit includes at least one multi-channel switching valve, at least one peristaltic pump, and at least one liquid level monitor, and is controlled by the control unit; The separation unit includes at least two series separation column systems consisting of actinide columns and glucose gel columns, wherein the separation column systems are connected to the pipeline in parallel. Piping units, including rigid pipes, flexible pipes and fittings connecting the various units; The control unit controls the channel switching of the multi-channel switching valve and the start / stop and flow rate of the peristaltic pump to achieve automatic switching, delivery and alternating work-regeneration cycles of the solution between parallel separation column systems.

2. The separation and purification system according to claim 1, characterized in that: The multi-channel switching valve includes at least two eight-channel switching valves and at least four three-channel switching valves. Through programming control of the control unit, the flow path can be switched between flowing through the separation column system and direct connection.

3. The separation and purification system according to claim 2, characterized in that: The control unit also includes a database for storing system operating parameters, equipment status information, and event logs in a time-series manner to ensure the traceability of operating data.

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