CN114937516A - A method for producing 68Ge based on accelerator irradiation - Google Patents

Abstract

The invention discloses a production method based on accelerator irradiation ⁶⁸ A method of Ge. The method comprises the following steps: s1, preparing a metal gallium-nickel alloy target, and then dissolving the metal gallium-nickel alloy target after irradiation; the structure of the metal gallium nickel alloy target is 1) or 2) as follows: 1) at least comprises two layers including a metal substrate layer and a metal gallium nickel alloy layer; 2) at least comprises three layers including a metal substrate layer, a metal protection layer and a metal gallium nickel alloy layer; s2, introducing the dissolved solution into a double-tandem chromatographic column for separation and purification, and collecting the solution containing ⁶⁸ A solution of Ge; s3, the obtained mixture contains ⁶⁸ Introduction of Ge solution ⁶⁸ Ge/ ⁶⁸ In a Ga generator, when ⁶⁸ After the Ge is fully adsorbed, eluting with an eluent pair at preset intervals ⁶⁸ Ge/ ⁶⁸ Eluting the separation column in the Ga generator, and collecting eluted eluate to obtain ⁶⁸ Ga products. The invention ⁶⁸ The separation and purification process of Ge has clear thought, simple operation, easy realization of automatic separation and purification, and high purityOf radioactive concentration ⁶⁸ Ge。

Description

A method for producing 68Ge based on accelerator irradiation

technical field

The invention relates to a method for producing and preparing ⁶⁸ Ge based on accelerator irradiation, and belongs to the technical field of positron tomography.

Background technique

At present, the production and separation processes for ⁶⁸ Ge at home and abroad are mainly based on solvent extraction, fractionation and chromatography. In the solvent extraction and separation process, organic reagents with high toxicity and carcinogenicity, such as carbon tetrachloride and toluene, are often used as extractants to extract and separate ⁶⁸ Ge. In addition, the solvent extraction was carried out under the condition of high acidity, which made ⁶⁸ Ge easily form ⁶⁸ GeCl ₄ aerosol, resulting in a large loss of ⁶⁸ Ge. Another process for separating and purifying ⁶⁸ Ge is fractional distillation, which is mainly based on the extremely volatile characteristics of ⁶⁸ GeCl ₄ (boiling point: 82-84°C) in acidic solution, and uses heating to remove ⁶⁸ Ge from irradiated target and other impurity nuclides. However, the recovery rate of ⁶⁸ Ge produced by this process is low, and it is easy to cause leakage of radioactivity and contamination.

Chromatography is a common separation method for separating ⁶⁸ Ge, which can realize the operation of continuous separation of ⁶⁸ Ge, which is very beneficial to the design and control of automatic separation, and at the same time, can avoid a large amount of loss of ⁶⁸ Ge. However, as far as the chromatographic separation process is concerned, the concentration and purity of the ^{68 Ge separated and purified are relatively low. Therefore, how to establish a 68 Ge} that can obtain high radioactive concentration and specific activity and can be compounded for medical use, and at the same time can be scaled It is important to automate the chromatographic process for the production of ⁶⁸ Ge.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a method for producing ⁶⁸ Ge by irradiating a metal gallium-nickel alloy target with an accelerator, and to establish a double chromatographic column series separation process that can be reused by Chelex100 and a glucose gel separation column. The process is applied to an automatic separation system, and a ⁶⁸ Ge product is successfully obtained; the method of the invention is simple and easy to implement, the principle of the automatic system is simple, the operation is convenient, and the large-scale production of ⁶⁸ Ge is easy to be realized.

The present invention first provides a ⁶⁸ Ge separation automation system, including a liquid taking unit, a conveying unit, a monitoring unit, a pH value regulating unit, a separation unit, a collection unit and a control unit;

The liquid taking unit and the collecting unit include several liquid storage containers and liquid conveying pipelines; the conveying unit includes at least one peristaltic pump and four multi-channel switching valves; the monitoring unit includes at least one liquid level sensor; the pH value regulating unit includes at least one pH value A monitor and a syringe pump with a switching valve head; the separation unit includes at least two identical or different separation columns; the collection unit includes a number of collection containers and a liquid recovery pipeline; the control unit includes a host computer, a programmable logic controller (PLC) ), control software and communication protocols, etc.;

The control unit controls the first multi-channel switching valve to rotate to a preset channel to absorb the solution in the liquid storage container of the liquid-taking unit; the first multi-channel output end is connected to the peristaltic pump input end, and the peristaltic pump output end is connected to the second multi-channel switch The valve input end, the output end of the second multi-channel switching valve is connected to at least two same or different separation column inlets, the separation column outlet is connected to the input end of the third multi-channel switching valve, the second and third switching valves are freely rotated through the control unit Make it flow through the separation column or not flow through the separation column; the output end of the third multi-channel switching valve is connected to the input end of the fourth multi-channel switching valve, and the output end of the fourth multi-channel switching valve is connected to the collection unit of the collection unit. container, the fourth multi-channel switching valve is used to introduce the liquid passing through the separation column into the corresponding recovery pipeline and enter the collection unit; the liquid level sensor of the monitoring unit is connected between the first multi-channel switching valve and the peristaltic pump, used for Monitor whether the control unit completely extracts the solution; the pH monitor and the syringe pump with the switching valve head in the pH control unit are used to connect to the collection container of the collection unit to adjust the pH of the solution ;

The multi-channel switching valve is at least a six-channel switching valve;

The liquid in the liquid storage container at least includes a dissolving solution of the irradiated metal gallium nickel target, a hydrochloric acid solution, an alkaline solution, a 0.001mol/L-1.5mol/L sodium citrate alkaline solution and deionized water;

At least one spare separation column system is included.

On the basis of the ⁶⁸ Ge separation automation system, the present invention provides a method for producing and preparing ⁶⁸ Ge based on an accelerator irradiated metal gallium-nickel alloy target, comprising the following steps:

S1, prepare a metal gallium nickel alloy target, and then dissolve it after irradiation;

The structure of the metal gallium nickel alloy target is as follows 1) or 2):

1) At least two layers are included, including a metal base layer and a metal gallium-nickel alloy layer;

2) At least three layers are included, including a metal base layer, a metal protective layer and a metal gallium nickel alloy layer;

S2. Pass the dissolved solution into double series chromatographic columns for separation and purification, and collect the solution containing ⁶⁸ Ge;

Described double series chromatographic column is the Chelex100 separation column and glucose gel separation column that are connected in series;

S3. Pass the obtained solution containing ⁶⁸ Ge into the ⁶⁸ Ge/ ⁶⁸ Ga generator, and after the ⁶⁸ Ge is fully adsorbed, use the eluent for the ⁶⁸ Ge/ ⁶⁸ Ga generator every preset time. The separation column in the medium is rinsed, and the rinsed eluent is collected to obtain ⁶⁸ Ga product.

In the above method, in step S1, the material of the metal first base layer is Cu or Al, which is a metal with strong electrical conductivity, high thermal conductivity and high hardness;

The metal protective layer is made of Au or Pt, with a thickness of at least 5 μm, and is an inert metal with strong electrical and thermal conductivity;

In the metal gallium nickel alloy layer, the mass content of Ga is not less than 50%, and the thickness is greater than 10 mg/cm ² .

In the above method, in step S1, the metal gallium-nickel alloy layer is prepared by an electroplating method;

The plating solution used can be an acidic solution, the acidity is 0.001-2 mol/L, the temperature is 25-100°C, the current density is 10-60 mA/cm ² , the molar concentration ratio of gallium ion to nickel ion is 1-10, and the stirring speed is 5～500rpm.

The proton accelerator is used for irradiation, the energy is 10-70MeV, the current intensity is 10-500μA, the time is not less than 1h, and the cooling time is at least 20 days.

In the above method, in step S2, a mixed system of an acidic solution and hydrogen peroxide is used for dissolving, wherein the concentration of the acidic solution is greater than 10 mol/L, the concentration of the hydrogen peroxide is 10-30%, and the dissolving temperature is 25-150 ° C;

The target solution after dissolving and irradiating is a clear and transparent solution, and the solution contains at least ⁶⁸ Ge, ^{68, nat} Ga, ⁵⁶ , 57, 58 Co, ⁶⁵ Zn, ^nat Ni and ^nat Cu.

In the above-mentioned method, in step S2, the condition of described separation and purification is as follows:

After the dissolved solution of the metal gallium nickel target is adjusted to a pH value of 1.0 to 5.0, it is passed into the Chelex 100 separation column, and the hydrochloric acid solution with a pH of 1.0 to 5.0 is used for rinsing, and the eluate is collected; Add 0.6-1.5 mol/L sodium citrate solution to the eluent, adjust the pH value to 10.0-13.0, and then pass it into the glucose gel separation column, and adopt 0.001-1.5 mol/L and pH of 10.0-1.5 mol/L. 10.0-13.0 sodium citrate solution, pH 10.0-13.0 alkaline solution and deionized water are successively rinsed; finally, 0.1-2.0 mol/L hydrochloric acid solution is used to pass into the glucose gel separation column, desorb and collect ⁶⁸ Ge products.

In the above-mentioned method, in step S2, after the separation and purification, hydrochloric acid, deionized water, sodium hydroxide and deionized water are successively introduced into the Chelex 100 separation column to regenerate it;

The glucose gel separation column can be directly reused without further processing.

In the above method, in step S2, the separation and purification are controlled by the ⁶⁸ Ge separation automation system.

In the above-mentioned method, in step S3, the filler material used in the separation column described in the ⁶⁸ Ge/ ⁶⁸ Ga generator is a metal oxide or an oxide-based organic resin (such as a silica-based benzene resin). triphenol resin, etc.).

The structure of the ⁶⁸ Ge/ ⁶⁸ Ga generator is as follows: the separation column is arranged in the shielding layer; the two ends of the separation column are respectively connected to the liquid inlet hose and the liquid outlet hose, and the liquid inlet hose and The liquid outlet hose is respectively connected with the syringe and the collection bottle through the through-plate joint;

The syringe is connected to a hose through a luer connector, the hose is connected to the through-board connector, and the liquid is transported into the separation column by squeezing the syringe, and the ⁶⁸ Ga product enters the separation column after passing through the separation column. collected in a collection bottle;

The shielding layer includes a lead shielding layer and a generator housing.

In the above method, in step S3, the solution containing ⁶⁸ Ge is passed into the separation column in the ⁶⁸ Ge/ ⁶⁸ Ga generator after adjusting the acidity (0.5-2.0 mol/L).

This can be accomplished by determining the radiochemical purity, radionuclear purity, and chemical purity ^of68Ga , the labeling of which is used to verify the ^{availability of68Ga} .

The present invention has the following advantages due to the adoption of the above technical solutions:

The separation and purification process of the ⁶⁸ Ge of the present invention is clear in idea, simple in operation, easy to realize automatic separation and purification, and obtains ⁶⁸ Ge of high purity and radioactive concentration. The designed automatic separation and purification system can realize multiple separation columns in series and can be used as a backup separation system, which effectively ensures the reliability and safety of the use of the automatic separation and purification system. The design of the ⁶⁸ Ge/ ⁶⁸ Ga generator is simple and easy to operate, and the obtained ⁶⁸ Ga has high purity, which can be applied to the preparation of radiopharmaceuticals.

Description of drawings

Figure 1 is a schematic diagram of the automated separation of ⁶⁸ Ge

Figure 2 is the general diagram of the connection of various components in the ⁶⁸ Ga automatic separation system.

FIG. 3 is a flow chart of the method for producing and preparing ⁶⁸ Ge by irradiating a metal gallium-nickel alloy target according to the present invention.

Figure 4 is a photograph of a metallic gallium-nickel alloy target.

Figure 5 is the γ spectrum before and after separation of ⁶⁸ Ge.

Figure 6 is a ⁶⁸ Ge/ ⁶⁸ Ga generator.

Figure 7 is a gamma spectrum of the ⁶⁸ Ga product.

Figure 8 is a graph of the radiochemical purity of ⁶⁸ Ga products determined by thin-layer chromatography.

Detailed ways

The experimental methods used in the following examples are conventional methods unless otherwise specified.

The materials, reagents, etc. used in the following examples can be obtained from commercial sources unless otherwise specified.

Example 1. Automated separation system for preparing ⁶⁸ Ge by irradiating metal gallium-nickel alloy targets

The automated separation system for separating and purifying ⁶⁸ Ge includes a liquid taking unit, a conveying unit, a monitoring unit, a pH control unit, a separation unit, a collection unit and a control unit.

The liquid taking unit and the collecting unit include several liquid storage containers and liquid conveying pipelines; the conveying unit includes at least one peristaltic pump and four multi-channel switching valves; the monitoring unit includes at least one liquid level sensor; the pH value regulating unit includes at least one pH value A monitor and a syringe pump with a switching valve head; the separation unit includes at least two identical or different separation columns; the collection unit includes a number of collection containers and a liquid recovery pipeline; the control unit includes a host computer, a programmable logic controller (PLC) ), control software and communication protocols, etc.;

The control unit of the automatic separation system controls the first multi-channel switching valve VA to rotate to a preset channel to extract the solution in the liquid storage container of the liquid-taking unit; the output end of the first multi-channel switching valve VA is connected to the input end of the peristaltic pump P1, and the peristaltic pump P The output end is connected to the input end of the second multi-channel switching valve VB, the output end of the second multi-channel switching valve VB is connected to the inlets of at least two identical or different separation columns C1 and C2, and the outlets of the separation columns C1 and C2 are connected to the third multi-channel switching valve The VC input end is freely rotated by the control unit to make it in two states of flowing through the separation column or not flowing through the separation column; the output end of the third multi-channel switching valve VC is connected to the input end of the fourth multi-channel switching valve VD. The output end of the four multi-channel switching valve VD is connected to the collecting container of the collecting unit, and the fourth multi-channel switching valve VD is used to introduce the liquid passing through the separation column into the corresponding recovery pipeline and enter the collecting unit. The liquid level sensor D of the monitoring unit is connected between the first multi-channel switching valve VA and the peristaltic pump P1 for monitoring whether the control unit completely extracts the solution. The pH monitor E with the probe G and the syringe pump P2 with the switching valve head in the pH control unit are used to connect to the collection container of the collection unit to adjust the pH of the solution, as shown in Figure 1.

Separation columns C1 and C2 include at least two identical or different separation columns.

The VA switching valve is preferably a ten-channel switching valve. The VA0 channel is connected to the input end of the peristaltic pump, the VA1-9 are connected to the respective liquid reservoirs of the liquid taking units A1-9, and the VA10 is connected to the collection unit B1 bottle.

The VB and VC switching valves are preferably six-channel switching valves. The output end of the peristaltic pump P1 is connected to the VB0 channel, the VB1 channel is directly connected to the VC1 channel, the VB5, 6 and VC5, 6 are respectively connected to the separation column through the connection, and the VB2, 3, 4 and VC2, 3, 4 are separated as a separate column. Alternate channel.

The VD switching valve is preferably a ten-channel switching valve. The VC0 channel is connected with the VD0 channel, and the VD1-10 is connected with each liquid storage container of the collecting unit B1-10.

A1-9 is preferably used to hold metal gallium-nickel target dissolving solution, hydrochloric acid solution with pH value of 1～5, hydrochloric acid solution with concentration of 0.5～3.0mol/L, sodium citrate solution of 0.25mol/L, 0.6～ 1.5mol/L sodium citrate solution (pH10.0～13.0), 0.001～0.1mol/L sodium citrate solution (pH10.0～13.0), pH 10.0～13.0 alkaline solution, deionized water, 1 ~5mol/L sodium hydroxide solution.

B1 is preferably used for holding 0.6-1.5mol/L sodium citrate solution, B2 is preferably used for ⁶⁸ Ge products, B3 is preferably used for holding radioactive waste liquid, and B4 is preferably used for holding non-radioactive waste liquid. B5~10 are used as backup collection containers.

The connection relationship of the equipment is shown in Figure 2. The multi-channel switching valve, liquid level sensor and peristaltic P1 are connected in series by the liquid pipeline. The switching valve, peristaltic pump P1, syringe pump P2, liquid level sensor and pH monitor communicate with PLC through communication cables. The modules are connected, and the state of the internal output register of the PLC and the state of each executive element establish a one-to-one correspondence through configuration. 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.

The specific operation process is as follows:

In the initial state, no command is input, the multi-channel switching valve is in the automatic reset state, and P1 and P2 are in the stop state. Input the command to the upper computer to make VA turn to VA8 position, VB to VB1 position, VC to VC1, VD to VD4, so that the liquid pipeline is connected from left to right. Enter the command to open P1 to remove air from the line.

Enter the ⁶⁸ Ge separation and purification steps into the control program and start executing:

The first step, activate the C1 column, input the command, make the liquid pipeline conduct according to VA2-VB5-VC5-VD4, open P1 and keep it for a period of time, activate the column G1, and connect the tail fluid to B4;

The second step, activate the C2 column, input the command, first make the liquid pipeline conduct according to VA4-VB1-VC1-VD4, open P1 and keep it for a period of time, then conduct according to VA4-VB6-VC6-VD4, open P1 and keep it After a period of time, the liquid pipeline is finally turned on according to VA5-VB6-VC6-VD4, and the tail fluid is connected to B4;

Step 3, C1 column purifies ⁶⁸ Ge, enter the command to make the liquid pipeline conduct according to VA2-VB1-VC1-VD4, and open P1 for a period of time, then make the liquid pipeline conduct according to VA1-VB5-VC5-VD1 Turn on P1 and keep it for a period of time, make the liquid pipeline conduct according to VA2-VB5-VC5-VD1, carry out the sample loading operation, and connect the tail fluid to B1. Then, the liquid pipeline is rinsed according to VA3-VB5-VC5-VD3, and the tail fluid is connected to B3;

Step 4, pH value adjustment, input command, turn on P2, adjust pH value;

Step 5, C2 column purifies ⁶⁸ Ge, input the command, first, make the liquid pipeline conduct according to VA5-VB1-VC1-VD3, open P1 and keep it for a period of time, the tail liquid is connected to B3; then, make the liquid pipeline press VA5-VB6-VC6-VD3 is turned on, P is turned on and kept for a period of time, and the tail fluid is connected to B3. Then, make the liquid pipeline conduct according to VA10-VB6-VC6-VD3, carry out the sample loading operation, and connect the tail fluid to B3. Furthermore, make the liquid pipeline conduct VA5-VB6-VC6-VD3 in sequence, and simultaneously open P1 for a period of time, make the liquid pipeline conduct according to VA6-VB6-VC6-VD3, and simultaneously open P1 for a period of time, Make the liquid pipeline conduct according to VA7-VB6-VC6-VD3, and open P1 at the same time for a period of time, make the liquid pipeline conduct according to VA8-VB6-VC6-VD4, and open P1 for a period of time at the same time to carry out the rinsing operation , the tail liquid is connected to B3; finally, the liquid pipeline is connected according to VA2-VB6-VC6-VD2, the elution operation is carried out, ⁶⁸ Ge is desorbed, and the tail liquid is connected to B2;

Step 6, C1 column regeneration, enter the command, first make the liquid pipeline conduct according to VA8-VB1-VC1-VD3. Turn on P1 and keep it for a period of time, the tail liquid is connected to B3; then make the liquid pipeline follow VA8-VB5 -VC5-VD3 is turned on, open P1 and keep it for a period of time, make the liquid pipeline follow VA9-VB5-VC5-VD3, and open P1 for a period of time at the same time, make the liquid pipeline follow VA8-VB5-VC5-VD3, and at the same time Turn on P1 for a period of time, and the tail fluid is connected to B3.

After the above steps are completed, the bottles B2, B3 and B4 respectively contain the product ⁶⁸ Ge product, radioactive waste liquid and non-radioactive waste liquid.

The redundant channels, redundant pipelines and empty bottles of the switching valve are used as backup to ensure the stability and reliability of the entire automatic separation system.

Example 2. Preparation of ⁶⁸ Ga based on accelerator irradiation

The flow chart is shown in Figure 3.

S1. Preparation and irradiation of metal gallium-nickel alloy target

In this step, the metal gallium nickel alloy target is prepared by an electrodeposition method.

Metal copper or metal aluminum is selected as the metal base layer, the thickness can be any thickness, and the size can be any size. In this embodiment, the metal base layer is preferably a metal copper block with a size of 11×3×0.5mm. The metal base layer is wrapped with an inert metal by electroplating. The inert metal in this embodiment is preferably gold, with a thickness of 5 μm. Prepare a mixed solution of GaCl ₃ and NiCl ₂ with a molar concentration ratio of 1:10 (pH value is 0.5-3.0), at a current density of 10 to 60 mA/cm ² , a temperature of 25 to 100 ° C and a stirring speed of 10 to 500 rpm. electroplating.

In this embodiment, the molar concentration ratio is preferably 4, the pH value is 1.5, the current density is 31 mA/cm ² , the temperature is 50° C. and the stirring speed is 300 rpm. The prepared metal gallium-nickel alloy target is shown in FIG. 4 .

The metal gallium-nickel alloy target is placed at the end of the proton accelerator for irradiation. The beam current and the target surface can be at any angle, the energy is 10-70MeV, the current intensity is 10-500μA, and the irradiation time is more than 1h. The irradiated target is cooled for a period of time and then dissolved and separated.

In this embodiment, the angle between the beam and the target surface is preferably 10°, the beam energy is 20MeV, the current intensity is 100μA, and the irradiation time is 10h.

Separation and purification of S2 and ⁶⁸ Ge

Dissolution of the S2.1 target

The irradiated metal gallium nickel alloy target is placed in a mixed system of acid and hydrogen peroxide. The acid solution can be one of sulfuric acid, nitric acid and hydrochloric acid or a mixed solution, the concentration is greater than 10mol/L, and the concentration of hydrogen peroxide is 10-30%. After it is completely dissolved, the pH value is adjusted to 1.0-5.0 with an alkaline solution. In this embodiment, the preferred acidic solution is sulfuric acid, the alkaline solution is sodium hydroxide solution, and the pH value is adjusted to 2.0-3.0.

Separation and purification of S2.2 ⁶⁸ Ge

First, separate columns one and two are activated. Secondly, pass the target solution into the separation column one, and wash the separation column one with an acidic solution with a pH of 3.0, and collect all the eluents at the same time. As shown in Fig. 5 (top and middle) before and after the separation column, the matrix elements and most of the impurity nuclides are removed. Add sodium citrate solution with a concentration of 0.6-1.5mol/L to the collected eluent, adjust the pH value of the eluent to 10.0-13.0, pass it into the separation column 2, and use a solution with a pH value of 10.0-13.0. Rinse with 0.001-1.5mol/L sodium citrate solution, and then rinse with alkaline solution with a concentration of less than 0.1mol/L and deionized water. The hydrochloric acid solution with a certain volume concentration of 0.1-0.001 mol/L was used to analyze ⁶⁸ Ge, and finally a ⁶⁸ Ge product with a volume of 5-20 mL was obtained. Figure 5 (bottom) is the γ energy spectrum obtained through separation column 2. It can be seen that all impurity nuclides have been removed. Finally, 5mCi of ⁶⁸ Ge was obtained with a recovery rate of 70%.

In this embodiment, the packing resin of the first separation column is preferably Chelex 100 resin. In this implementation, the preferred resin of the second separation column is glucose gel resin G25, and the preferred volume of the ⁶⁸ Ge product is 10-20 mL.

S2.3 ⁶⁸ Ge/ ⁶⁸ Ga generator

⁶⁸ Ge/ ⁶⁸ Ga generator, including shielding layer, syringe, connecting joint, inlet and outlet hoses, through-plate joint, separation column and collection bottle, as shown in Figure 6.

The shielding layer includes the generator housing 1 and the lead shielding layer 2 with brackets. Among them, the inlet and outlet of the separation column are connected with the liquid inlet and outlet hoses through male thread straight-through joints 4 and 7 and placed in the lead shielding layer 2 with brackets. The syringe 13 is connected to the hose through the luer connector 12, and the hose is connected to the liquid inlet hose of the separation column 5 through the through-plate connector 11, and the solution is delivered to the separation column 5 by squeezing the syringe. The liquid outlet hose 10 of the separation column 5 is communicated with the generator casing through the through-plate joint 8 , and conveys the waste liquid or ⁶⁸ Ga product of the assembled generator to the collection bottle 9 . Wherein, the packing material 6 in the separation column is mainly metal oxides (such as tin oxide, titanium oxide, vanadium oxide, tantalum oxide, etc.) or an organic resin based on a certain oxide (for example, a silica-based resin). Phloroglucinol resin, etc.), the preferred filling material in this embodiment is tin oxide, and the particle size is 100-300 mesh. Wherein, the separation column diameter ratio is 10-5:1, preferably 7:1 in this embodiment.

The steps of assembling the ^68Ge / ^68Ga generator are as follows: pass the ^68Ge solution with the adjusted acidity into the installed separation column, and select the hydrochloric acid solution of the corresponding acidity for rinsing, and use the hydrochloric acid solution about every 4-5h. The generator is rinsed to obtain ⁶⁸ Ga product.

Quality inspection of S2.4 ⁶⁸ Ga

It can be seen from the γ energy spectrum of ⁶⁸ Ga (Fig. 7) that no γ energy peaks of other impurity nuclides are found, and ⁶⁸ Ga has a high radionuclear purity, which can reach 99.9%. The radiochemical purity was determined by thin-layer chromatography. As shown in Figure 8, the radiochemical purity was greater than 99%. Measured by ICP-OES, the ^68Ga product contains Sn less than 1ppm, which is in line with medical standards.

In order to verify the availability of ⁶⁸ Ga, the obtained ⁶⁸ Ga product was further purified and then labeled with DOTATATE and PSMA-617, and the labeling rate could reach more than 92%.

Claims (10)

1. A kind of ⁶⁸ The automatic Ge separation system comprises a liquid taking unit, a conveying unit, a monitoring unit, a pH value regulating and controlling unit, a separating unit, a collecting unit and a control unit;

the control unit controls the first multi-channel switching valve to rotate to a preset channel to suck the solution in the liquid storage container of the liquid taking unit; the output end of the first multi-channel is connected with the input end of a peristaltic pump, the output end of the peristaltic pump is connected with the input end of a second multi-channel switching valve, the output end of the second multi-channel switching valve is connected with the inlets of at least two same or different separation columns, the outlets of the separation columns are connected with the input end of a third multi-channel switching valve, and the second and third switching valves are freely rotated by the control unit to be in two states of flowing through the separation columns or not flowing through the separation columns; the output end of the third multi-channel switching valve is connected with the input end of a fourth multi-channel switching valve, the output end of the fourth multi-channel switching valve is connected with the collection container of the collection unit, and the fourth multi-channel switching valve is used for introducing the liquid passing through the separation column into the corresponding recovery pipeline and entering the collection unit. A liquid level sensor of the monitoring unit is connected between the first multi-channel switching valve and the peristaltic pump and used for monitoring whether the control unit completely extracts the solution; and a pH value monitor and a syringe pump with a switching valve head in the pH value regulating and controlling unit are connected in a collecting container of the collecting unit and used for regulating the pH value of the solution.

2. Production and preparation of metallic gallium-nickel alloy target based on accelerator irradiation ⁶⁸ Method of Ga comprising the steps of:

s1, preparing a metal gallium nickel alloy target, and then dissolving the metal gallium nickel alloy target after irradiation;

the structure of the metal gallium nickel alloy target is 1) or 2) as follows:

1) at least comprises two layers including a metal substrate layer and a metal gallium nickel alloy layer;

2) at least comprises three layers including a metal substrate layer, a metal protective layer and a metal gallium-nickel alloy layer;

s2, introducing the dissolved solution into a double-tandem chromatographic column for separation and purification, and collecting the solution containing ⁶⁸ A solution of Ge;

the double tandem chromatographic columns at least comprise a Chelex100 separation column and a glucose gel separation column which are connected in series;

s3, the obtained mixture contains ⁶⁸ Introduction of Ge solution ⁶⁸ Ge/ ⁶⁸ In a Ga generator, when ⁶⁸ After the Ge is fully adsorbed, the leaching solution is used for leaching the Ge at preset time intervals ⁶⁸ Ge/ ⁶⁸ Leaching the separation column in the Ga generator, and collecting leached leacheate to obtain ⁶⁸ Ga products.

3. The method of claim 2, wherein: in step S1, the material of the metal first substrate layer is Cu or Al;

the metal protective layer is made of Au or Pt and has the thickness of at least 5 mu m;

in the metal gallium-nickel alloy layer, the Ga mass content is not less than 50%, and the thickness is more than 10mg/cm ² 。

4. A method according to claim 2 or 3, characterized in that: in step S1, preparing the metal gallium-nickel alloy layer by an electroplating method;

and (3) irradiating by using a proton accelerator, wherein the energy is 10-70 MeV, the flow intensity is 10-500 muA, and the time is not less than 1 h.

5. The method according to any one of claims 2-4, wherein: in the step S2, a mixed system of an acidic solution and hydrogen peroxide is adopted for dissolution, wherein the concentration of the acidic solution is greater than 10mol/L, the concentration of the hydrogen peroxide is 10-30%, and the dissolution temperature is 25-150 ℃.

6. The method according to any one of claims 2-5, wherein: in step S2, the separation and purification conditions are as follows:

adjusting the pH value of the solution obtained after the metal gallium nickel target is dissolved to 1.0-5.0, introducing the solution into the Chelex100 separation column, leaching the solution by adopting a hydrochloric acid solution with the pH value of 1.0-5.0, and collecting leacheate; simultaneously adding 0.6-1.5mol/L sodium citrate solution into the leacheate, adjusting the pH value to 10.0-13.0, introducing the glucose gel separation column, and leaching by adopting 0.001-1.5 mol/L, pH of 10.0-13.0 sodium citrate solution, 10.0-13.0 alkaline solution and deionized water in sequence; finally, introducing 0.1-2.0 mol/L hydrochloric acid solution into the glucose gel separation column, desorbing and collecting ⁶⁸ And (4) Ge product.

7. The method of claim 6, wherein: in step S2, after the separation and purification, hydrochloric acid, deionized water, sodium hydroxide, and deionized water are sequentially introduced into the Chelex100 separation column to regenerate the column.

8. The method according to any one of claims 2-7, wherein: in step S2, the method according to claim 1 ⁶⁸ And the Ge separation automation system controls the separation and purification.

9. The method according to any one of claims 2-8, wherein: in step S3, the ⁶⁸ Ge/ ⁶⁸ The packing material adopted by the separation column in the Ga generator is metal oxide or organic resin taking oxide as matrix.

10. The method according to any one of claims 2-9, wherein: in step S3, the product contains ⁶⁸ The solution of Ge is introduced into the reactor after the acidity is adjusted ⁶⁸ Ge/ ⁶⁸ In the separation column in a Ga generator.

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