Method for preparing germane-68

Abstract

The invention provides a method for preparing germane-68. The method comprises the steps that a gallium-containing alloy layer of a target piece is irradiated through a proton beam, the thickness of the gallium-containing alloy layer ranges from 1 mm to 5 mm, and the energy of protons ranges from 30 MeV to 100 MeV; dissolving the irradiated gallium-containing alloy layer to obtain an alloy layer solution; and extracting the germane-68 from the alloy layer solution. According to the method, the yield of the germane-68 is increased.

Description

Technical Field

[0001] The present application relates to the field of preparation of radioactive nuclides, and in particular to a method for preparing germanium-68. Background Art

[0002] Gallium-68 (Ga-68 or 68 Ga) is the labeling nuclide of many radiopharmaceuticals (abbreviated as radiopharmaceuticals). At present, 13 types of Ga-68 labeled radiopharmaceuticals have entered clinical use in China, and their application prospects are broad. Ga-68 is mainly prepared by germanium-68 / gallium-68 generators. Among them, the parent nuclide germanium-68 (Ge-68 or 68 Ge, half-life 288 days) decays to produce the daughter nuclide gallium-68 (half-life 68 minutes), thus providing gallium-68 for a longer period of time. In addition, Ge-68 can also be used as a long-life positron source for attenuation correction and calibration of positron electron scanners (PET). Therefore, in June 2021, the National Atomic Energy Agency, together with eight ministries and commissions including the State Administration of Science, Technology and Industry for National Defense, jointly issued the "Medium- and Long-Term Development Plan for Medical Isotopes" (2021-2035). Among the key tasks, the "Plan" clearly states the need to complete the research and development of key technologies for the irradiation and separation preparation of a series of new medical isotopes including Ge-68 by accelerators, as well as the construction of supporting capabilities.

[0003] The yield and impurity elements of the reaction for preparing germanium-68 are affected by the nuclear reaction route, the material and thickness of the target, the energy of the irradiated particle beam, and many other factors. The type and content of impurities in the product are also affected by the purification and extraction method. In the nuclear reaction route, germanium-68 can be prepared from natural gallium, germanium, and zinc. Usually, germanium-68 is prepared from gallium. The corresponding nuclear reaction is nat Ga(p,xn) 68 Ge, the irradiation particle beam is a proton beam. In terms of targets, since the melting point of metal gallium is very low (29.8°C), it cannot be used directly as an irradiation target. Currently, the melting point is usually increased by preparing gallium-containing alloys. When gallium-containing alloys are used as targets, the energy of the proton beam currently used is about 20 to 30 MeV, corresponding to the maximum value of the above-mentioned nuclear reaction cross section.

[0004] At present, the yield of germanium-68 prepared by using gallium-containing alloy targets still has room for improvement. Therefore, it is necessary to provide an improved process for preparing germanium-68. Summary of the invention

[0005] In view of this, the main purpose of the present disclosure is to provide a method for preparing germanium-68, which can increase the yield of germanium-68.

[0006] In order to achieve the above objectives, the present disclosure provides the following technical solutions.

[0007] The present disclosure provides a method for preparing germanium-68, comprising irradiating a gallium-containing alloy layer of a target with a proton beam, wherein the gallium-containing alloy layer has a thickness of 1 mm to 5 mm and the energy of the proton is 30 MeV to 100 MeV; dissolving the irradiated gallium-containing alloy layer to obtain an alloy layer solution; and extracting germanium-68 from the alloy layer solution. The present application uses a medium-to-high energy proton beam to irradiate a thick gallium-containing alloy layer, which can increase the yield of germanium-68 to more than 0.020 mCi / μA·h, reduce side reactions during irradiation, produce less impurity nuclides, and simplify the subsequent process of extracting germanium-68.

[0008] According to some embodiments, the energy of the proton is 60 MeV to 90 MeV, which is more conducive to increasing the yield of germanium-68 while reducing impurity nuclides.

[0009] According to some embodiments, the energy of the proton is 70 MeV to 80 MeV.

[0010] According to some embodiments, the gallium-containing alloy layer has a thickness of 2 mm to 4 mm. This is more conducive to increasing the stability of the target and improving the yield of germanium-68.

[0011] According to some embodiments, the gallium-containing alloy layer has a thickness of 2.5 mm to 3.5 mm.

[0012] According to some embodiments, the angle between the proton beam and the gallium-containing alloy layer is 5° to 15°, which is more conducive to increasing the effective irradiation thickness of the target.

[0013] According to some embodiments, the angle between the proton beam and the gallium-containing alloy layer is 6° to 10°.

[0014] According to some embodiments, the proton beam intensity is 10 μA to 600 μA.

[0015] According to some embodiments, the proton beam intensity is 50 μA to 200 μA. This is more conducive to maintaining the stability of the target while increasing the yield.

[0016] According to some embodiments, the irradiation time is 10 h to 100 h.

[0017] According to some embodiments, in the gallium-containing alloy, the weight percentage of gallium is 10% to 90%.

[0018] According to some embodiments, the weight percentage of gallium is 70% to 80%. This is more conducive to making the target withstand the above-mentioned medium and high energy proton beam irradiation while increasing the gallium loading in the target.

[0019] According to some embodiments, the gallium-containing alloy further comprises one or more of nickel, indium, tin, iron, ruthenium, osmium, chromium, rhenium, molybdenum, tungsten, manganese, cobalt, and rhodium. This is more conducive to increasing the melting point of the gallium-containing alloy layer, so that it can withstand the above-mentioned medium and high energy proton beam irradiation and increase stability.

[0020] According to some embodiments, the gallium-containing alloy is composed of gallium and nickel, which is more conducive to reducing impurity nuclides.

[0021] According to some embodiments, the target is obtained by a step including pressing the gallium-containing alloy into a groove of a metal-based target holder of the target by hot pressing, wherein the depth of the groove is 1 mm to 5 mm. In the above manner, the gallium-containing alloy prepared in advance is pressed into the target holder groove of the above depth, and the gallium-containing alloy layer formed is firmly bonded to the target holder, can withstand a fall from a height of 5 meters, and can withstand the above medium and high energy proton beam irradiation, the target has good stability, and the gallium loading in the target is increased.

[0022] According to some embodiments, dissolving the irradiated gallium-containing alloy layer includes electrolyzing the target in an inorganic acid to dissolve the irradiated gallium-containing alloy layer. The electrolysis can reduce the concentration of the acid used for target dissolution, avoid heating operations, and shorten the target dissolution time.

[0023] According to some embodiments, the inorganic acid is hydrochloric acid, which is beneficial to the dissolution of the gallium-containing alloy layer.

[0024] According to some embodiments, the concentration of the inorganic acid is 1 mol / L to 5 mol / L, which is beneficial for dissolving the gallium-containing alloy layer.

[0025] According to some embodiments, extracting germanium-68 from the alloy layer solution includes extracting germanium-68 through iminodiacetic acid chelating resin and dextran gel resin in sequence, thereby facilitating obtaining germanium-68 that meets the requirements of medical germanium-68 products.

[0026] The present invention achieves an increase in the yield of germanium-68 by irradiating a thickened gallium-containing alloy layer with a medium-to-high energy proton beam.

[0027] In addition to the technical problems solved by the present disclosure, the technical features that constitute the technical solutions, and the beneficial effects brought about by the technical features of the technical solutions described above, other technical problems that can be solved by the present disclosure, other technical features included in the technical solutions, and the beneficial effects brought about by these technical features will be further described in detail in the following specific embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the conventional technology, the drawings required for use in the embodiments or the conventional technology descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0029] Figure 1 The preparation of Example 1 of the present disclosure is shown 68 Schematic diagram of the process flow of Ge.

[0030] Figure 2 The gallium-nickel alloy prepared by high-temperature melting in Example 1 of the present disclosure is shown.

[0031] Figure 3 The target piece produced by hot pressing a gallium-nickel alloy onto a copper target holder in Example 1 of the present disclosure is shown.

[0032] Figure 4 A high-purity germanium gamma spectrometer diagram of the alloy layer solution of Example 1 of the present disclosure is shown.

[0033] Figure 5 The prepared Example 1 of the present disclosure is shown 68 GeCl 4 High purity germanium gamma spectrometer of the solution. DETAILED DESCRIPTION

[0034] The technical solution of the present disclosure will be clearly and completely described below in conjunction with specific implementations and drawings. Obviously, the described implementations are only part of the implementations of the present disclosure, not all of the implementations. Based on the implementations in the present disclosure, all other implementations obtained by ordinary technicians in the field without creative work are within the scope of protection of this application.

[0035] Throughout the specification, unless otherwise specifically stated, the terms used herein should be understood as meanings commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. In the event of a conflict, this specification takes precedence.

[0036] It should be noted that in the present disclosure, the term "comprising" or any other variant thereof is intended to cover non-exclusive inclusion, so that a method or device including a series of elements includes not only the elements explicitly stated, but also other elements not explicitly listed, or also includes elements inherent to the implementation of the method or device. In the absence of further restrictions, an element defined by the phrase "comprising..." does not exclude the presence of other related elements in the method or device including the element.

[0037] Except in any operating examples, or where otherwise indicated, all numerals used in the specification and claims indicating component amounts, reaction conditions, etc. should be understood to be modified by the term "approximately" in all cases. Unless otherwise indicated, the numerical parameters set forth in the following specification and the appended claims are approximate values, which can vary according to the desired properties to be obtained by the present disclosure. Although the numerical ranges and parameters setting forth the broad scope of the present disclosure are approximate values, the numerical values ​​set forth in the specific embodiments are reported as accurately as possible.

[0038] The above steps are divided only for clear description. When implemented, they can be combined into one step or some steps can be split and decomposed into multiple steps. As long as they include the same logical relationship, they are all within the protection scope of this patent.

[0039] At present, in the process of preparing germanium-68 using a target with a gallium-containing alloy layer, the gallium-containing alloy layer is usually prepared by electroplating. The obtained gallium-containing alloy layer is relatively firmly bonded to the target, but the yield of germanium-68 is not satisfactory. The inventors have found that the thickness of the gallium-containing alloy layer obtained by the electroplating method is difficult to exceed 0.5 mm. When a lower energy proton beam is used for irradiation, there are more side reactions, resulting in the production of more impurity nuclides. When a higher energy proton beam is used for irradiation, the proton beam easily penetrates the gallium-containing alloy layer and hits the target holder, which also produces more impurity nuclides. The yield of germanium-68 produced by these two methods is low. Moreover, if medical germanium-68 with extremely high purity requirements is to be obtained, the required separation and purification steps are cumbersome and the equipment cost is high.

[0040] For example, CN105308687A relates to a process for generating germanium, which discloses the use of a 29 MeV proton beam with a beam current of about 185 μA for 4.4 days of irradiation, and then stripping the irradiated target with an acidic mixture multiple times to form a stripping solution. Since the operation cannot be closed, a special ventilation device is required to capture germanium tetrachloride; then a non-polar solvent is used to extract germanium radioactive isotopes from the stripping solution through a cumbersome procedure and wash; then solid phase extraction and water extraction are performed to obtain a Ge-68 product, and finally 68 The output of Ge is 0.005 mCi / μA·h. CN114937516A relates to a method for preparing a catalytic converter based on accelerator irradiation. 68 Ge method, which discloses the use of electroplating to prepare a gallium-nickel alloy layer, the accelerator energy is 20MeV, the beam intensity is 100μA, the target is irradiated for 10 hours, and an acid solution and hydrogen peroxide mixed system are used for dissolution, wherein the concentration of the acid solution must be greater than 10mol / L, the concentration of the hydrogen peroxide is 30%, and it needs to be heated to above 70°C, and finally separated by CHELEX-100 resin and dextran gel resin G25 to obtain 68Ge, the yield is 0.005mCi / μA·h. These methods cannot achieve satisfactory yield and product purity.

[0041] Therefore, there is still a need to provide an improved method for preparing germanium-68 to increase the yield of germanium-68.

[0042] Based on this, the present application provides a method for preparing germanium-68. The present application and optional implementation methods are described in more detail below.

[0043] The method for preparing germanium-68 provided in the present application includes: irradiating a gallium-containing alloy layer of a target with a proton beam, wherein the thickness of the gallium-containing alloy layer is 1 mm to 5 mm, and the energy of the protons is 30 MeV to 100 MeV; dissolving the irradiated gallium-containing alloy layer to obtain an alloy layer solution; and extracting germanium-68 from the alloy layer solution.

[0044] The present application can increase the yield of germanium-68 to more than 0.020mCi / μA·h by irradiating a gallium-containing alloy layer with a thickness of 1mm to 5mm with a medium-high energy 30MeV to 100MeV proton beam. At the same time, the method has few side reactions during irradiation, and the probability of the proton beam penetrating the gallium-containing alloy layer is small, and the impurity nuclides produced are small, so that the subsequent extraction of germanium-68 only involves conventional separation adsorption resins, and the process is simplified.

[0045] The present disclosure has no particular restrictions on the preparation of gallium-containing alloys. Those skilled in the art can prepare them according to equipment and methods known in the art, such as melt metallurgy, extrusion, powder metallurgy, and solution co-precipitation. Preferably, the preparation of gallium-containing alloys by melt metallurgy is convenient for controlling the weight percentage of gallium and obtaining a thick and uniform alloy layer. For example, the preparation of gallium-containing alloys by melt metallurgy includes: heating a crucible containing a plurality of metals including metallic gallium in a specific proportion and a specific purity in a high-temperature vacuum melting furnace and an inert gas atmosphere, melting at a temperature of 100°, and obtaining a gallium-containing alloy block after cooling.

[0046] According to some embodiments, in the gallium-containing alloy, the weight percentage of gallium is 10% to 90%. Exemplarily, the weight percentage of gallium is 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or a value between the ranges formed by any two values, but not limited thereto. Preferably, the weight percentage of gallium is 70% to 80%. Thus, it is more conducive to making the target withstand the above-mentioned medium and high energy proton beam irradiation while increasing the gallium loading in the target.

[0047] According to some embodiments, the gallium-containing alloy further includes one or more of nickel, indium, tin, iron, ruthenium, osmium, chromium, rhenium, molybdenum, tungsten, manganese, cobalt, and rhodium. This is more conducive to increasing the melting point of the gallium-containing alloy layer, so that it can withstand the above-mentioned medium and high energy proton beam irradiation and increase stability.

[0048] According to some embodiments, the gallium-containing alloy is composed of gallium and nickel, which is more conducive to reducing impurity nuclides.

[0049] According to some embodiments, the thickness of the gallium-containing alloy layer is 1 mm to 5 mm. Exemplarily, the thickness of the gallium-containing alloy layer is 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, or a value between the ranges formed by any two values, but is not limited thereto. Preferably, the thickness of the gallium-containing alloy layer is 2 mm to 4 mm. Thus, it is more conducive to increasing the stability of the target while increasing the yield of germanium-68. More preferably, the thickness of the gallium-containing alloy layer is 2.5 mm to 3.5 mm.

[0050] According to some embodiments, the target is obtained by a step including pressing the gallium-containing alloy into a groove of a metal-based target holder of the target by hot pressing, wherein the depth of the groove is 1 mm to 5 mm. The target comprises a metal-based target holder and a gallium-containing alloy laminate, wherein the gallium-containing alloy laminate is embedded in the groove of the metal-based target holder; the shape, size, and depth of the groove on the metal-based target holder correspond to the shape, size, and depth of the gallium-containing alloy layer, thereby forming a specific gallium-containing alloy layer after hot pressing. The present disclosure has no particular restrictions on the material of the metal-based target holder, which may be copper, aluminum, nickel, steel, and / or other conductive materials. Preferably, the material of the metal-based target holder may be copper, which produces less impurities after the above-mentioned medium- and high-energy proton beam irradiation, and its high thermal conductivity facilitates the effective transfer of heat away from the target body, and its high electrical conductivity facilitates the subsequent operation of the irradiated gallium-containing alloy layer by electrolytic dissolution. The gallium-containing alloy prepared in advance is pressed into the target holder groove of the above-mentioned depth by hot pressing. The gallium-containing alloy layer formed is firmly bonded to the target holder and can withstand falling from a height of 5 meters and the above-mentioned medium and high energy proton beam irradiation. The target has good stability and the gallium loading in the target is increased.

[0051] The target needs to be well cooled during irradiation, and close contact between the gallium-containing alloy laminate and the target holder is necessary. In some embodiments, the temperature of hot pressing is 100°C to 400°C, and the pressure is 20 tons to 60 tons. In some embodiments, annealing is performed at 300°C to 700°C for 3 to 7 hours after hot pressing. This is conducive to forming a close bond between the gallium-containing alloy laminate and the target holder.

[0052] Those skilled in the art can irradiate the gallium-containing alloy layer of the target with a proton beam according to equipment and methods known in the art. Exemplarily, the target is placed in an irradiation target station, and irradiation conditions such as the irradiated proton energy, beam intensity, and the angle between the proton beam intensity and the gallium-containing alloy layer are set. In order to avoid local overheating of the irradiated target and oxidation or melting, a high-current proton beam with uniform beam modulation is used to irradiate the target. During the irradiation process, a certain flow rate of water cooling is set on the back of the target holder, and a certain flow rate of air cooling is set on the front. After irradiation, the target is cooled for a period of time to allow most of the short-lived nuclides to decay. Subsequently, the target can be placed in a lead tank through a target removal device, transported to a hot chamber, and the irradiated gallium-containing alloy layer is dissolved to extract germanium-68.

[0053] When the gallium-containing alloy layer of the target is irradiated with a proton beam, the energy of the proton is 30MeV to 100MeV. Exemplarily, the energy of the proton is 30MeV, 40MeV, 50MeV, 60MeV, 70MeV, 80MeV, 90MeV, 100MeV or a value between the ranges consisting of any two values, but not limited thereto. Preferably, the energy of the proton is 60MeV to 90MeV. Thus, it is more conducive to increasing the yield of germanium-68 while reducing impurity nuclides. More preferably, the energy of the proton is 70MeV to 80MeV.

[0054] According to some embodiments, when the gallium-containing alloy layer of the target is irradiated with a proton beam, the angle between the proton beam and the gallium-containing alloy layer is 5° to 15°. As a result, it is more conducive to increasing the effective irradiation thickness of the gallium-containing alloy layer. Exemplarily, the angle between the proton beam and the gallium-containing alloy layer is 5°, 6°, 7°, 8°, 9°, 10°, 11°, 12°, 13°, 14°, 15° or a value between the ranges consisting of any two values, but not limited thereto. Preferably, the angle between the proton beam and the gallium-containing alloy layer is 6° to 10°, and more preferably, 7° to 9°.

[0055] According to some embodiments, the beam current intensity of the protons is 10μA to 600μA. Exemplarily, the beam current intensity of the protons is 10μA, 30μA, 50μA, 100μA, 150μA, 200μA, 250μA, 300μA, 350μA, 400μA, 450μA, 500μA, 550μA, 600μA or a value between the ranges consisting of any two values, but not limited thereto. Preferably, the beam current intensity of the protons is 50μA to 200μA. Thus, it is more conducive to maintaining the stability of the target while increasing the yield.

[0056] According to some embodiments, the irradiation time is 10h to 100h. Exemplarily, the irradiation time is 10h, 20h, 30h, 40h, 50h, 60h, 70h, 80h, 90h, 100h or a value between any two values, but not limited thereto. Preferably, the irradiation time is 20h to 80h. Thus, it is more conducive to maintaining the stability of the target while increasing 68 Each output.

[0057] The gallium-containing alloy layer of the target is usually dissolved using a high concentration of acid, such as hydrochloric acid, nitric acid and / or sulfuric acid of more than 5 mol / L, which takes a long time to dissolve under heating, usually more than 24 hours, and the dissolution is incomplete. Due to the properties of germanium and its compounds, radioactive aerosols are easily generated during the above heating process. Therefore, as a radioactive operation, the above dissolution process is slow and difficult.

[0058] According to some embodiments, dissolving the irradiated gallium-containing alloy layer includes electrolyzing the target in an inorganic acid to dissolve the irradiated gallium-containing alloy layer. Exemplarily, the target is taken out and assembled on an electrochemical dissolution tank as an anode, and a metal such as nickel, copper or platinum is used as a cathode. A dilute inorganic acid is added to the tank, and the power supply is turned on after setting the voltage at room temperature until the gallium-nickel alloy layer is completely dissolved. In this way, the concentration of the acid used for dissolving the target can be reduced, heating operation can be avoided, and the target dissolution time can be shortened.

[0059] According to some embodiments, the concentration of the inorganic acid is 1 mol / L to 5 mol / L. This is beneficial to the dissolution of the gallium-containing alloy layer. Exemplarily, the concentration of the inorganic acid is 1 mol / L, 2 mol / L, 3 mol / L, 4 mol / L, 5 mol / L, or a value between any two values, but not limited thereto. Preferably, the concentration of the inorganic acid is 2 mol / L to 4 mol / L.

[0060] The inorganic acid may be selected from hydrochloric acid, sulfuric acid and nitric acid. According to some embodiments, the inorganic acid is hydrochloric acid. Thus, the dissolution of the gallium-containing alloy layer is facilitated.

[0061] The ions in the alloy layer solution obtained after dissolution include, in addition to Ge, impurities such as Ga, Cu, Ni, Zn, Co, and Fe. The impurity elements in the final product are not only affected by various factors in the above-mentioned preparation reaction process, but also related to the subsequent purification and extraction method. At present, the purification methods include extraction, distillation, resin separation and adsorption, etc. In particular, medical germanium-68 products require Ge-68 nuclear purity> 99.9%. At the same time, in terms of chemical purity, for each mCi of radioactivity, the content of cobalt (Co), copper (Cu), iron (Fe), nickel (Ni), lead (Pb), zinc (Zn), and niobium (Nb) is less than 1μg, and the content of gallium (Ga) is less than 2μg, which puts higher requirements on the process of extracting germanium-68. At present, when using special extraction or distillation methods, the steps are cumbersome, and the extraction method requires the use of highly toxic and carcinogenic organic reagents. The distillation method requires high temperature conditions. In addition, extraction and distillation cannot be closed and require the use of special equipment. The method of the present application uses a medium-to-high energy proton beam to irradiate a gallium-containing alloy layer target having a thickness of 1 mm to 5 mm, which can effectively reduce the impurity nuclides produced after irradiation, so that the subsequent purification method can obtain medical germanium-68 only through conventional separation and adsorption resins.

[0062] According to some embodiments, in the method of the present application, the alloy layer solution is sequentially passed through an iminodiacetic acid chelating resin and a dextran gel resin to extract germanium-68, and germanium-68 is extracted from the alloy layer solution. The iminodiacetic acid chelating resin can adsorb most impurities such as Ga, Cu, Ni, Zn, Co, and Fe, and the dextran gel resin can specifically adsorb Ge. The germanium-68 separated by using the above two resins can meet the requirements of medical germanium-68 products. Exemplarily, the pH of the alloy layer solution is increased with an alkaline solution, and a solution filled with an iminodiacetic acid chelating resin (e.g. CH-90, Chelex 100, etc.), collect the eluent, further increase its pH with an alkaline solution, and then pass it into a chromatography column 2 filled with a dextran gel resin (such as Sephadex G25), wash a small amount of residual impurities with a dilute alkaline solution, and finally elute the adsorbed 68 Ge, get 68 Ge solution.

[0063] Example

[0064] Hereinafter, the embodiments of the present application will be described. The embodiments described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. If no specific techniques or conditions are indicated in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. If the manufacturer is not indicated in the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0065] Example 1

[0066] according to Figure 1 The schematic diagram of the process shown is the preparation 68 Ge, the specific steps are as follows.

[0067] Target preparation

[0068] Weigh 40g of metallic gallium (purity: 99.999%) and 10g of metallic nickel (purity: 99.95%) into an alumina crucible, cover it with a lid, put it into a high-temperature melting furnace (manufacturer: Zhengzhou Kejia Electric Furnace Co., Ltd., model: KJ-V1400-6LZ), evacuate to below 10Pa, introduce high-purity argon gas, repeat three times, exhaust the air in the furnace, and finally set the temperature rise program to 10°C / min under the high-purity argon atmosphere, start heating, and melt at 1200°C for 3h. After cooling, a gallium-nickel alloy is obtained. Figure 2 shown.

[0069] The gallium-nickel alloy was placed in an elliptical groove with a depth of 3 mm in an oxygen-free copper target holder using a fully automatic hot pressing machine (manufacturer: Tianjin Jingtuo Instrument Technology Co., Ltd., model: PCH-600DG), and pressed at 300°C with a pressure of 30 tons. Then, the target was annealed at 500°C for 5 hours, and after cooling, the surface of the gallium-nickel alloy in the groove was trimmed to obtain a target with a gallium-nickel alloy layer with a thickness of 3 mm, such as Figure 3 shown.

[0070] Irradiation target

[0071] The gallium-nickel alloy layer of the above target is placed on the irradiation target station at an angle of 7.5° with the proton beam direction, and a beam monitoring and temperature control monitoring system is installed. With a proton beam spot of 75MeV and 40mm energy, a proton beam with an energy of 75MeV and a beam intensity of 100μA is obtained through a collimator (short axis 13mm, long axis 40mm, thickness 50mm). The target is irradiated for 20 hours, and the cooling water flow rate of the water cooling strip on the back of the target holder is 10L / min. The irradiated target is taken out of the target station and placed to cool for 90 days.

[0072] Electrochemical dissolution of irradiated gallium-nickel alloy layer

[0073] The cooled target was transferred to the hot chamber using a shielded lead can, and the target was taken out and assembled on the electrochemical dissolution tank. 100 mL of hydrochloric acid (3 mol / L) was added to the tank. The target was the anode and the platinum sheet was the cathode. The dissolution voltage was set to 3 V, and the constant voltage and constant current power supply was powered on for 2 hours. When the current suddenly dropped to about 1 A, the gallium-nickel alloy layer of the target was completely dissolved to obtain 100 mL of alloy layer solution. The alloy layer solution was detected by a high-purity germanium γ spectrometer (manufacturer: American ORTEC, model: GEM-35190-S), as shown in FIG. Figure 4As shown, 68 The characteristic peaks corresponding to Ge are 511keV and 1077.3keV. The alloy layer solution contains 68 The activity of Ge accounts for 0.24 of the total radionuclide activity.

[0074] extract 68 Ge extraction

[0075] The pH of the alloy layer solution was adjusted to 2.5 with 10 mol / L sodium hydroxide solution. The chromatography column 1 (with an inner diameter of 30 mm and a length of 200 mm) was filled with CH-90 chelating resin, use a peristaltic pump to transport the alloy layer solution to the chromatography column 1, control the flow rate to 2mL / min, then rinse with 50mL of hydrochloric acid solution with a pH of 2.5, collect 150mL of eluent; add 100mL of 1mol / L sodium citrate buffer with a pH of 12.5 to the eluent, adjust the pH to 12.5 with 10mol / L sodium hydroxide solution, and obtain 68 Ge crude product liquid. CH-90 chelating resin can be rinsed and regenerated with 5% dilute sulfuric acid solution and recycled for reuse.

[0076] The above 68 The Ge crude product solution was transported to the chromatography column 2 (10 mm in inner diameter and 60 mm in length), which was filled with Sephadex G25 dextran gel resin and the flow rate was controlled at 2 mL / min. Then, it was rinsed with 1 mol / L sodium citrate solution (pH = 12.5), 0.001 mol / L sodium citrate solution (pH = 12.5), 0.03 mol / L sodium hydroxide solution (pH = 12.5) and high-purity water in sequence, and finally, the adsorbed was eluted with 20 mL of 0.1 mol / L dilute hydrochloric acid. 68 Ge, get 68 GeCl 4 Solution.

[0077] Product quality testing

[0078] The above was detected by radioactivity meter (manufacturer: CAPINTEC.INC., model: CRC-25R). 68 GeCl 4 The total activity of the solution is 70mCi, and the radioactivity concentration is 3.5mCi / mL.

[0079] According to GB T 11713-2015 General method for high purity germanium gamma spectrum analysis, the product is tested by high purity germanium gamma spectrometer, such as Figure 5As shown, no γ energy peaks of other impurity nuclides were found (detection limit 0.5Bq), and the Ge-68 nuclear purity was greater than 99.996%, which is significantly higher than the Ge-68 nuclear purity requirement for general medical germanium-68 products.

[0080] According to HJ700-2014 water quality 65 elements determination inductively coupled plasma mass spectrometry, the metal impurity content in the product was detected by ICP-MS (manufacturer: Perkin Elmer, model: NexION 1000G). The results are shown in Table 1 below. For each mCi of radioactivity, the contents of cobalt, copper, iron, nickel, lead, zinc, niobium, etc. are all less than 1μg, and the gallium content is less than 2μg, which meets the chemical purity requirements of medical germanium-68 products.

[0081] Table 1.

[0082] Test items Content (μg / mL) Chemical purity (μg / mCi) Co <0.01 <0.003 Cu 0.021 0.006 Fe <1.0 <0.286 Ni 0.023 0.007 Pb <0.01 <0.003 Zn <1.0 <0.286 Nb <0.01 <0.003 Ga 4.55 1.300

[0083] Comparative Example 1

[0084] Germanium-68 was prepared in the same manner as in Example 1 except that: GaCl 3 and NiC1 2 Dissolve in 0.1M hydrochloric acid to form an electroplating solution, in which the concentration of gallium ions is 1mol / L and the concentration of nickel ions is 0.25mol / L. Pour the electroplating solution into the electroplating tank, with the platinum sheet as the anode and the copper target holder as the cathode, and the flow density is 40mA / cm 2 The target with a gallium alloy layer thickness of 0.300 mm was obtained after 6 hours of electroplating. After 20 hours of 20 MeV proton beam irradiation, the target was dissolved and detected by a high-purity germanium gamma spectrometer. 68 The activity of Ge accounts for 0.13 of the total radioactive nuclide activity, and many impurity nuclides are produced. 68 The proportion of Ge is much smaller than that in Example 1. After separation and purification 68 GeCl 4 The solution yield is 0.009 mCi / μA·h, and the Ge-68 core purity is 96.9%.

[0085] The above descriptions are only some specific embodiments of the present disclosure, which are intended to illustrate the present disclosure and are not intended to limit the scope of protection claimed in the present application. All modifications, substitutions, or direct / indirect applications in other related technical fields made using the contents of the present application description and drawings under the inventive concept of the present disclosure are included in the scope of protection claimed in the present application.

Claims

1. A method for preparing germanium-68, comprising: Irradiating the gallium-containing alloy layer of the target with a proton beam, wherein the gallium-containing alloy layer has a thickness of 1 mm to 5 mm and the energy of the protons is 30 MeV to 100 MeV; dissolving the irradiated gallium-containing alloy layer to obtain an alloy layer solution; and Germanium-68 is extracted from the alloy layer solution.

2. The method according to claim 1, characterized in that The energy of the proton is 60MeV to 90MeV; preferably, the energy of the proton is 70MeV to 80MeV.

3. The method according to claim 1, characterized in that The thickness of the gallium-containing alloy layer is 2 mm to 4 mm; preferably, the thickness of the gallium-containing alloy layer is 2.5 mm to 3.5 mm.

4. The method according to claim 1, characterized in that: The included angle between the proton beam and the gallium-containing alloy layer is 5° to 15°; preferably, the included angle between the proton beam and the gallium-containing alloy layer is 6° to 10°.

5. The method according to claim 1, characterized in that The proton beam current intensity is 10 μA to 600 μA; preferably, the proton beam current intensity is 50 μA to 200 μA.

6. The method according to claim 1, characterized in that The irradiation time is 10h to 100h.

7. The method according to claim 1, characterized in that In the gallium-containing alloy, the weight percentage of gallium is 10% to 90%; preferably, the weight percentage of gallium is 70% to 80%; preferably, the gallium-containing alloy also includes one or more of nickel, indium, tin, iron, ruthenium, osmium, chromium, rhenium, molybdenum, tungsten, manganese, cobalt, and rhodium; preferably, the gallium-containing alloy consists of gallium and nickel.

8. The method according to claim 1, characterized in that The target is obtained by a step of pressing the gallium-containing alloy into a groove of a metal-based target holder of the target by hot pressing, wherein the depth of the groove is 1 mm to 5 mm.

9. The method according to claim 1, characterized in that: Dissolving the irradiated gallium-containing alloy layer comprises electrolyzing the target in an inorganic acid to dissolve the irradiated gallium-containing alloy layer; preferably, the inorganic acid is hydrochloric acid; preferably, the concentration of the inorganic acid is 1 mol / L to 5 mol / L.

10. The method according to claim 1, characterized in that Extracting germanium-68 from the alloy layer solution comprises extracting germanium-68 through iminodiacetic acid chelating resin and dextran gel resin in sequence.

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