Systems and methods for producing germanium-68 isotopes

Abstract

A system and method for producing the germanium-68 (Ge-68) isotope is provided. The method includes irradiating a plated or encapsulated target containing gallium, dissolving the irradiated target in acid, and purifying the dissolved target by distillation to produce purified Ge-68. A melting cell assembly is provided for use in the melting step of the method.

Description

[Technical Field]

[0001] The present invention relates to a system and method for producing germanium-68 (Ge-68) isotope. [Background technology]

[0002] There are existing methods for producing Ge-68, which typically involve either extraction or chromatography.

[0003] Solvent extraction is a method of separating compounds based on their relative solubilities in two different immiscible liquids, such as a nonpolar solvent and a polar solvent. Examples of nonpolar solvents are carbon tetrachloride and organic solvents such as hexane.

[0004] Solvent extraction requires the use of carbon tetrachloride. The Food and Drug Administration (FDA) classifies carbon tetrachloride as a toxic and carcinogenic solvent, and the FDA suggests avoiding Class 1 solvents. See Figure 1A for prior art extraction methods. Examples of polar solvents are water and ethanol. Disadvantages of extraction include the potential presence of trace amounts of Class 1 toxic solvents in the product, the fact that extraction is a manual, intensive procedure, and the production of dissolved target waste and toxic solvent waste.

[0005] Another method used to produce Ge-68 is column chromatography, a method of separating materials based on the differential adsorption of compounds to an adsorbent. Each compound moves at a different rate through the column. See Figure 1B for a prior art chromatography method. Disadvantages of chromatography include the potential presence of trace amounts of starting and target materials in the product, such as cobalt (Co), gallium (Ga), nickel (Ni), and zinc (including but not limited to Zn-65); column chromatography is a manual-intensive procedure; and dissolved target and solvent waste is generated. Summary of the Invention [Problem to be solved by the invention]

[0006] Therefore, there is a need for a system and method for producing Ge-68 isotope, particularly medical-grade Ge-68 isotope, that overcomes the shortcomings of these known methods. [Means for solving the problem]

[0007] The present invention relates to a method for producing germanium-68 (Ge-68) isotopes, preferably medical-grade Ge-68 isotopes.

[0008] In one embodiment of the present invention, a method for producing Ge-68 isotope is provided, the method comprising the steps of irradiating a Ga-Ni alloy plated solid target to form an irradiated Ga-Ni alloy plated target, dissolving the irradiated Ga-Ni alloy plated solid target in acid, and purifying the dissolved irradiated plated target by distillation to produce purified Ge-68.

[0009] In one embodiment of the present invention, a method for producing the Ge-68 isotope is provided, comprising irradiating gallium metal encapsulated in a metal or metal alloy to form an irradiated encapsulated target, heating the irradiated target to melt the Ga metal, drilling holes in the heated target, dissolving the drilled target in acid, and purifying the melted target by distillation to produce purified Ga-68.

[0010] In one embodiment of the present invention, a system for carrying out the method(s) is provided, the system including a lysis cell assembly including a lysis tank or tank assembly and a heater or heater assembly.

[0011] Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.

[0012] The present invention will become more fully understood from the detailed description and accompanying drawings, which are not necessarily to scale. [Brief explanation of the drawings]

[0013] [Figure 1A] This is a prior art extraction method. [Figure 1B] This is a prior art chromatographic method. [Figure 2] 1 is a system diagram according to the present invention; [Figure 3] FIG. 2 is another system diagram according to the present invention. [Figure 4A] Figure 2 is a perspective view of the dissolution cell assembly. [Figure 4B] Figure 4A is an exploded view of the lysis cell assembly. [Figure 4C] FIG. 1 is another view of the dissolution cell assembly of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0014] The following description of embodiments of the present invention is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses. The following description is provided herein merely by way of example for the purpose of providing an enabling disclosure of the invention, but is not intended to limit the scope or content of the invention.

[0015] In one embodiment of the present invention, a method for producing a germanium-68 (Ge-68) isotope, preferably a Ge-68 medical grade isotope, is provided.

[0016] In one embodiment of the present invention, the method generally includes the steps of providing a plated target, irradiating the plated target, melting the irradiated target, and purifying the melted target by distillation to obtain the Ge-68 isotope.

[0017] Target plating A solid metal is used as a base or base layer and plated with a Ga-Ni alloy, thereby forming a plated target. Alternatively, the plated target includes a base or base layer, an optional insulating layer, and a Ga-Ni alloy layer. Preferably, the base or base layer includes silver (Ag). However, other metals or metal alloys for the base layer include, but are not limited to, copper (Cu), aluminum (Al), nickel (Ni), tungsten (W), Ag-Cu alloy, W-Ag alloy, rhodium (Rh), Rh-Ga alloy, niobium (Nb), other thermally conductive metals or metal alloys, or combinations thereof. Metals or metal alloys for the insulating layer include, but are not limited to, silver (Ag), copper (Cu), aluminum (Al), nickel (Ni), tungsten (W), Ag-Cu alloys, W-Ag alloys, rhodium (Rh), Rh-Ga alloys, niobium (Nb), other thermally conductive metals or metal alloys, or combinations thereof.

[0018] Irradiation of plated targets : The plated target is sent to a cyclotron and irradiated to form an irradiated Ga-Ni alloy plated Ag solid target.

[0019] Melting of plated targets : An irradiated Ga-Ni alloy-plated silver solid target is placed in the melting cell assembly. The Ga-Ni alloy is melted using hydrochloric acid (HCl) at approximately 70-80°C for approximately 6 to 24 hours. The vapors produced during the melting process are condensed in a condenser and returned to the melting cell assembly.

[0020] Distillation purification of the productAfter dissolution is complete, change the valve settings and increase the temperature to approximately 90-100°C. Since germanium tetrachloride is the only volatile compound at approximately 95°C, the vapor is condensed in the distillation condenser and the purified Ge-68 product is collected in the receiver. Purification takes approximately 20-60 minutes.

[0021] In one embodiment of the present invention, a system is provided. Referring to Figures 2 and 3, the system includes a main body 10, a distillation condenser 20, a collection assembly 30, a receiver 40, a reflux condenser (without a valve) 50, a glass tube 60, a condenser holder 70, a dissolution cell assembly 80, and a base support stand(s) (preferably porcelain) 90. For example, as shown in Figure 3, the system has two condensers and a receiver connected to the main body. Both condensers can be separated from the condenser holder.

[0022] Figure 4A is a perspective view of the lysis cell assembly of Figure 2. Figure 4B is an exploded view of the lysis cell assembly of Figure 4A. Figure 4C is a photograph of a lysis cell assembly of the present invention.

[0023] The melting cell assembly 80 generally includes a melting tank or tank assembly and a heater or heater assembly, which typically includes a melting cell base heater assembly and a melting cell heater plug assembly.

[0024] As shown in the figure, the lysis cell assembly 80 includes a lysis cell crossbar subassembly 110, a lysis tank assembly 120, pipette adapter(s) 130, locating pin(s) 140, a lysis cell base heater assembly 150, cap(s) 160, a lysis cell heater plug assembly 170, columns 180, pipette tip(s) 190, 200, and stainless steel (SS) hex socket countersunk head screws 210, 220. The pipette tips 190, 200 are inserted through holes drilled in the lysis cell crossbar subassembly 110 into the pipette adapter 130, which is threaded into the lysis tank assembly 120. The holes in the lysis cell crossbar subassembly 110 align with holes in the lysis tank assembly 120. Two locating pins 140 are inserted into two holes in the lysis cell base heater assembly 150. Two columns 180 are also inserted into two holes in the dissolution cell base heater assembly 150. The columns 180 connect to the dissolution tank assembly 120 by inserting them through notches in the dissolution tank assembly 120. The dissolution cell heater plug assembly 170 is connected to the dissolution cell base heater assembly 150. Screws are used to connect each of the two columns 180 and two locating pins 140 to the dissolution cell base heater assembly 150. Screws 210 also thread through the cap 160 and into the dissolution cell crossbar subassembly 110.

[0025] The purpose of the melting cell assembly is to serve as a means to dissolve Ga-Ni alloy plated on an Ag target in a 4N to 12N HCl solution. The Ga-Ni alloy plating target is set up between the melting cell base heater assembly 150 and the melting tank assembly 120. Approximately 30 ml to 70 ml of 4N to 12N HCl is added to slowly dissolve the Ga-Ni alloy. Silver, fortunately, does not react with HCl. After the Ga-Ni alloy is completely dissolved, the solution is transferred to a round-bottom flask for the purification process.

[0026] The dissolving tank assembly 120 is constructed from glass or plastic. The preferred plastic is acrylic. However, other plastics may be used, including, but not limited to, polytetrafluoroethylene (PTFE), fluoroethylenepropylene (FEP), perfluoroalkoxy (PFA), ethylenetetrafluoroethylene copolymer (ETFE), ethylene-chlorotrifluoroethylene (E-CTFE), polyvinylidene fluoride (PVDF), polyvinyl fluoride (PVF), terephthalate (PET), polyethylene (PE), polyvinyl chloride (PVC), polypropylene (PP), or combinations thereof. Because Ge-68 tetrachloride is volatile, an optional vapor color indicator may be added to the pipette tip 190 for its presence. While the dissolving cell assembly 180 and the purification distillation condenser 20 are shown as separate units, it is within the scope of the present invention to combine the dissolving cell assembly 180 with the distillation condenser 120.

[0027] In one embodiment of the present invention, a method for producing Ge-68 isotope is provided, the method comprising the steps of providing an encapsulated target, irradiating the encapsulated target, melting the irradiated target, and purifying the melted target by distillation to obtain Ge-68 isotope.

[0028] Encapsulated TargetsGallium metal is encapsulated in a metal or metal alloy, thereby forming an encapsulated target. For example, 6 to 18 grams of Ga metal can be encapsulated in a niobium-zirconium alloy. This alloy can contain up to 50 weight percent zirconium. The encapsulated target is then irradiated. After irradiation is complete, the irradiated target is heated to 30 to 40°C to melt the Ga metal. The niobium alloy capsule is then punctured, and the liquid Ga is transferred to a flask, such as a 50 to 250 ml round-bottom flask. This method further includes melting the irradiated target, preferably in a melting cell assembly. Approximately 10 to 100 ml of 4N to 12N HCl and 10 to 100 ml of 30% H2O2 are added to the round-bottom flask. Dissolution is complete when all the Ga metal has been oxidized to the chloride form. The next step is to purify the melted target by distillation, similar to the Ge-68 solid target process.

[0029] Advantages of the system and method of the present invention include the absence of known impurities, the final product being the only volatile compound (excluding the solvents, which are HCl and water), a simple and efficient one-step purification, and minimal amounts of dissolved target waste but no solvent waste. [Example]

[0030] Two-hour, 50-200 μA, 29 MeV proton irradiations were conducted on 0.5-2.0 grams of GaNi alloy electroplated silver targets. A volume of 30-70 ml of 6N HCl was used to dissolve the GaNi alloy to form a dissolved target solution (DTS). A sample of the DTS was analyzed using gamma spectroscopy to generate the "before purification" data shown in Table 1. The DTS was then purified by distillation, and 5-10 ml of distillate was collected. A portion of the purified sample was analyzed using gamma spectroscopy to generate the "after purification" data.

[0031] [Table 1]

[0032] The % yield of Ge-68 was 97.7%. After purification, all non-Ge isotopes were undetectable (ND).

[0033] Thus, those skilled in the art will readily appreciate that the present invention is susceptible of broad utility and application. Many embodiments and adaptations of the present invention other than those described herein, as well as many variations, modifications, and equivalent arrangements, will be apparent or reasonably suggested from the present invention and the foregoing description thereof, without departing from the content or scope of the present invention. Thus, while the present invention has been described in detail herein in connection with preferred embodiments thereof, it should be understood that this disclosure is merely illustrative and exemplary of the invention and has been made solely for the purpose of providing a complete and enabling disclosure of the invention. The foregoing disclosure is not intended or construed to limit the invention or otherwise exclude any such other embodiments, adaptations, variations, modifications, and equivalent arrangements.

Claims

1. 1. A method for producing germanium-68 isotope, comprising: irradiating the Ga—Ni alloy plated solid target to form an irradiated Ga—Ni alloy plated target; dissolving the irradiated Ga—Ni alloy plated solid target in hydrochloric acid (HCl); purifying the molten irradiated plating target by distillation to produce purified germanium-68; A method comprising:

2. The method of claim 1 , wherein the solid target comprises silver.

3. The method of claim 1 , wherein the solid target is plated with an insulating layer.

4. 4. The method of claim 3, wherein the insulating layer is selected from the group consisting of copper, aluminum, nickel, tungsten, silver-copper alloy, tungsten-silver alloy, rhodium, rhodium-gallium alloy, niobium, and combinations thereof.

5. 10. The method of claim 1, wherein the dissolution occurs at a temperature in the range of 70°C to 80°C.

6. The method of claim 1 further comprising the step of condensing vapors produced during dissolution.

7. The method of claim 1 further comprising increasing the temperature after dissolution.

8. The method of claim 7, wherein the temperature is increased to 90°C to 100°C.

9. The method of claim 6 , wherein the vapor is condensed in a distillation condenser.

10. The method of claim 1 further comprising collecting the purified Ge-68.

11. 11. The method of claim 10, wherein the purified Ge-68 is medical grade.

12. 1. A method for producing the Ge-68 isotope, comprising: irradiating gallium metal encapsulated within a metal or metal alloy to form an irradiated encapsulated target; heating the irradiated target to melt the Ga metal; drilling the heated target; dissolving the drilled target with hydrochloric acid (HCl); purifying the molten target by distillation to produce purified Ge-68; A method comprising:

13. The method of claim 12, wherein the metal alloy is a niobium-zirconium alloy.

14. The method of claim 13, wherein the niobium-zirconium alloy contains up to 50 weight percent zirconium.

15. The method of claim 12 , wherein the lysis occurs in a lysis cell assembly.

16. The lysing and purifying steps are performed in a lysis cell assembly, the lysis cell assembly comprising: a dissolving tank or tank assembly; Heater or heater assembly The method of claim 1 , comprising:

17. 17. The method of claim 16, wherein the heater or heater assembly comprises a dissolution cell base heater assembly and a dissolution cell heater plug assembly.

18. 18. The method of claim 17, further comprising a pipette tip.

19. 20. The method of claim 18, wherein a vapor color indicator is present in the pipette tip.

20. 17. The method of claim 16, wherein the dissolution cell assembly is combined with a distillation condenser.

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