Separation of rare earth elements by physical chemistry

Abstract

In particular, methods and systems for the periodic enrichment of rare earth elements and isotopes are provided. A crucible, or a tube or ampoule which may have two coaxially opposing crucibles in fluid communication, is used to hold a source material in a vacuum and irradiate the source material to enrich it with respect to a product material. Source material (e.g., 176 Irradiating with Yb-enriched Yb to produce a product (for example, 177 After obtaining Lu), the mixture may be sublimated to remove most of the source material and concentrate the product material by, for example, heating the lower part of the tube and cooling the upper part of the tube to condense the sublimated source material at the top of the tube. Subsequently, the concentrated product material may be purified, or the solidified source structure may be reused in an irradiation / sublimation cycle to further enrich and concentrate the product material.

Description

[Technical Field]

[0001] 1. Technical Fields This invention relates to the field of physical chemical methods for substance separation, and more particularly to systems and methods for separating lutetium (Lu) and ytterbium (Yb). [Background technology]

[0002] 2. Explanation of related technologies The following patents and patent applications are incorporated herein by reference in their entirety. 1. Gschneidner 1965 (The application of vacuum metallurgy in the purification of rare-earth metals, OSTI Technical report, Ames Lab., Iowa State University of Science and Tech., Vacuum Metallurgy Conference, New York) teaches vacuum melting and distillation separation processes for rare-earth metals and provides various reduction and purification techniques. 2. Russian Patent No. 2704005 teaches a method for producing the lutetium-177 radionuclide without a carrier by irradiating metallic ytterbium as the target material in a stream of thermal neutrons in a nuclear reactor. Separation of the target material is carried out by evaporating it to a ballast volume in a high vacuum at a temperature of 700-800°C, and the lutetium-177 radionuclide as a product of the reaction (Yb-176(n,γ) → Yb-177 → Lu-177) is left on the inside of the container and washed with a solution of hydrochloric acid or nitric acid. 3. International Publication No. 2019106182 teaches compounds of the following formula for the chromatographic separation of rare earth elements and / or s-, p-, d-metals. [ka] 4. International Publication No. 2021102167 and International Publication No. 2021202914 teach a method for purifying lutetium by preparing a solid composition containing ytterbium and lutetium, and sublimating or distilling the ytterbium from the solid composition at a temperature of about 1196°C to about 3000°C to leave a lutetium composition containing a higher weight percent of lutetium than that present in the solid composition. 5. U.S. Patent Application Publication No. 20240011125 teaches that a ytterbium composition is obtained from an initial solid composition containing ytterbium and lutetium by sublimation or distillation in an inert or reduced-pressure environment at a first mean temperature over a first sublimation / distillation time to leave a lutetium composition containing a higher weight percent of lutetium than that present in the initial solid composition; the ytterbium composition is collected; the ytterbium composition is held for a longer waiting time than the first sublimation / distillation time to form a decayed ytterbium composition; and after the waiting time, a purified ytterbium composition is obtained from the decayed ytterbium composition by sublimation or distillation in an inert or reduced-pressure environment at a second mean temperature over a second sublimation / distillation time to leave a waste composition. 6. U.S. Patent Application Publication No. 20240068071 describes a sublimation / distillation apparatus comprising a crucible having an open end, a heating device thermally coupled to the crucible, an actively cooled collection substrate positioned above the open end of the crucible, and a vacuum chamber housing the crucible, the heating device, and the actively cooled collection substrate. 7. U.S. Patent Application Publication No. 20240035118 describes a phase-change crucible comprising an inner chamber including an inner chamber wall extending from an inner chamber floor to the upper end of the inner chamber, and an outer chamber including an outer chamber wall extending from an outer chamber floor to the upper end of the outer chamber, wherein the upper end of the inner chamber terminates beyond the upper end of the outer chamber, and the outer chamber wall surrounds an inner collection area formed by the inner chamber wall and the inner chamber floor, and an outer collection area formed by the outer chamber wall, the inner chamber wall, and the outer chamber floor.

[0003] As will be discussed below, the disclosed embodiments have yield, safety, 177 It is advantageous over prior art in various aspects, such as the efficiency of Lu collection and / or the purity and / or concentration of the product. 177 Lu is useful in medical applications such as imaging or labeling tumors for therapeutic purposes. [Overview of the Initiative] [Means for solving the problem]

[0004] The following is a simplified overview that provides an initial understanding of the present invention. This overview does not necessarily identify any essential elements or limit the scope of the invention, but serves only as an introduction to the following description.

[0005] One aspect of the present invention is an enrichment system comprising a sealing unit configured to heat a tube to create a vacuum therein and subsequently (continuously) seal the tube, the tube being neutron-transmissive and heat-resistant up to at least 600 °C and containing a source material; an irradiation unit configured to irradiate the source material within the sealed tube with neutrons to enrich the source material with respect to product material therein; a sublimation unit configured to sublime the source material within the sealed tube to concentrate the product material within the sealed tube; and a handling unit configured to break the seal of the tube, separate the concentrated product material from the sublimated source material, and use the sublimated source material as the source material for a continuous enrichment cycle through the system.

[0006] One aspect of the present invention is to use the above enrichment system 177 to produce Lu, comprising the steps of irradiating a Yb source material within a sealed tube with neutrons to enrich the source material with respect to Lu product material; sublimating Yb from the irradiated source material to concentrate the Lu product material within the sealed tube; and repeating the irradiation using the sublimated Yb as the source material and the sublimation of Yb from the irradiated source material to further concentrate the Lu product material. 176 irradiating a Yb source material within a sealed tube with neutrons to enrich the source material with respect to 177 Lu product material; 176 sublimating Yb from the irradiated source material to concentrate the 177 Lu product material within the sealed tube; 176 using the sublimated Yb as the source material for irradiation and sublimating Yb from the irradiated source material 176 to further concentrate the 177 Lu product material.

[0007] One aspect of the present invention is a periodic 177 Lu production and separation method, comprising the steps of setting a first crucible having Yb in fluid communication coaxially opposite a second crucible, both crucibles being disposed within a tube, both the crucibles and the tube being transparent (neutron-transmissive); heating the tube to create a vacuum therein and subsequently sealing the tube; irradiating Yb within the first crucible within the sealed tube with neutrons 176 176 Yb with neutrons to​177 Enriched in Lu 176 The process of generating Yb, 176 Yb is sublimated from the first crucible to the second crucible, and in the first crucible 177 The process involves concentrating Lu in a sealed tube, and then breaking the seal of the tube and concentrating the Lu. 177 The first crucible containing Lu was sublimated. 176 The process of separating from the second crucible containing Yb and for the next cycle 176 Sublimation from each cycle to prepare the first crucible containing Yb 176 Using a second crucible containing Yb, the process of setting, heating, irradiating, sublimating and breaking is repeated multiple times, and the concentrated from the multiple cycles 177 Lu is post-processed and purified 177 The present invention provides a method that includes the step of obtaining Lu.

[0008] One aspect of the present invention is a periodic enrichment method comprising the steps of: setting up a first crucible having a source material in fluid communication with a second crucible, coaxially opposite each other, wherein both crucibles are set up inside a tube, and both crucibles and the tube are transparent (permeable) to neutrons; heating the tube to create a vacuum inside the tube, and then sealing the tube; irradiating the source material in the first crucible inside the sealed tube with neutrons to enrich the source material with respect to the product material therein; and sublimating the source material from the first crucible into the second crucible, thereby enriching the product material in the first crucible. The present invention provides a method comprising the steps of: concentrating in a sealed tube; breaking the seal of the tube and separating the first crucible containing the concentrated product material from the second crucible containing the sublimated source material; repeating the above steps of setting, heating, irradiating, sublimating, and breaking for multiple cycles using the second crucible containing the sublimated source material from each cycle to prepare the first crucible containing the source material for the next cycle; and post-processing the concentrated product material from the multiple cycles to obtain a purified product material.

[0009] One aspect of the present invention is an enrichment system comprising a sealing unit configured to heat a tube to create a vacuum inside the tube and then seal the tube, the tube comprising a first crucible having a source material, which is in fluid communication with a second crucible coaxially opposite the first crucible, both crucibles being set inside the tube, and both crucibles and the tube being transparent (permeable) to neutrons; an irradiation unit configured to irradiate the source material in the first crucible inside the sealed tube with neutrons to enrich the source material with respect to the product material therein; and a unit that moves the source material from the first crucible to the second crucible. The enrichment system includes a sublimation unit configured to concentrate the product material in a first crucible within a sealed tube, a handling unit configured to break the seal of the tube, separate the first crucible containing the concentrated product material from the second crucible containing the sublimated source material, and use the second crucible containing the sublimated source material as the first crucible containing the source material for a continuous enrichment cycle through the system, and a post-processing unit configured to obtain a purified product material from the concentrated product material from a plurality of enrichment cycles.

[0010] One aspect of the present invention is, 176 Yb 177 A system for converting to Lu, comprising a sealed tube under vacuum and a first open end, inside 176 A first crucible containing Yb source material and located within a sealed tube, and a second crucible located within a sealed tube and having a second open end, which is coaxially aligned with the first crucible and in fluid communication with it, with the second open end facing the first open end of the first crucible, and within a sealed tube 176 Irradiate the Yb source material with neutrons, 177 The system includes an irradiation unit configured to produce Lu product material, wherein the tube and both crucibles are made of a neutron-transparent material.

[0011] One aspect of the present invention is, 176 From the Yb source ingredients 177A method for preparing Lu product material, wherein in a sealed tube under vacuum 176 Irradiate the Yb source material with neutrons, 176 Sublimate the Yb sauce ingredients 177 The process includes the step of producing a Lu product material, and the sealed tube includes a first open end, and inside 176 The present invention provides a method comprising a first crucible containing Yb source material and a second crucible having a second open end and positioned within a sealed tube, wherein the first and second crucibles are coaxially aligned and in fluid communication within the sealed tube, with the second open end of the second crucible facing the first open end of the first crucible, and the tube and both crucibles are made of a neutron-transparent (permeable) material.

[0012] These additional and / or other aspects and / or advantages of the present invention are described in the following detailed description, may be inferred from the detailed description, and / or can be learned through the practice of the present invention. [Brief explanation of the drawing]

[0013] To better understand embodiments of the present invention and to show how embodiments of the present invention may be carried out, the accompanying drawings are to be referenced hereby purely as examples. In the accompanying drawings, similar numerical values ​​represent corresponding elements or parts throughout.

[0014] [Figure 1A] Figures 1A and 1B are high-level schematic block diagrams of an enrichment system in operation according to some embodiments of the present invention. [Figure 1B] Figures 1A and 1B are high-level schematic block diagrams of an enrichment system in operation according to some embodiments of the present invention.

[0015] [Figure 2A] Figures 2A to 2C are high-level flowcharts illustrating a periodic enrichment method according to several embodiments of the present invention. [Figure 2B]Figures 2A to 2C are high-level flowcharts illustrating a periodic enrichment method according to several embodiments of the present invention. [Figure 2C] Figures 2A to 2C are high-level flowcharts illustrating a periodic enrichment method according to several embodiments of the present invention.

[0016] [Figure 3] Figure 3 is a high-level schematic, non-limiting example of the operation of an enrichment system for periodic generation and separation of 177Lu according to some embodiments of the present invention.

[0017] [Figure 4] Figure 4 is a high-level schematic diagram of possible configurations and operating principles of a sealing unit in a tube sealing process according to some embodiments of the present invention.

[0018] [Figure 5A] Figure 5A is a high-level schematic diagram of a possible embodiment of a sublimation unit in a sublimation process of ytterbium as an example of a source material, according to some embodiments of the present invention.

[0019] [Figure 5B] Figure 5B provides a high-level schematic diagram of a sealed tube and the sublimation process therein, according to some embodiments of the present invention.

[0020] [Figure 6] Figure 6 is a high-level schematic diagram of possible configurations and operating principles of a handling unit in the process of breaking a sealed tube, according to some embodiments of the present invention.

[0021] [Figure 7]Figures 7A to 7C provide background information, including the decay scheme of the radionuclide 177Lu schematically shown in Figure 7A, the dependence of the yield of 177Lu on the irradiation time of 176Yb for different values ​​of neutron flux density schematically shown in Figure 7B, and the specific activity of 177Lu as a function of irradiation and duration of post-reactor storage / processing at different percentage contents of 174Yb in the starting isotope mixture schematically shown in Figure 7C.

[0022] To keep the explanation concise and clear, it should be understood that the elements shown in the diagrams are not necessarily drawn to scale. For example, the dimensions of some elements may be exaggerated relative to others for clarity. Furthermore, where deemed appropriate, reference numbers may be repeated across multiple diagrams to indicate corresponding or similar elements. [Modes for carrying out the invention]

[0023] The following description outlines various aspects of the present invention. For illustrative purposes, specific configurations and details are described in order to provide a complete understanding of the invention. However, it will be apparent to those skilled in the art that the invention may be carried out without the specific details presented herein. Furthermore, well-known features may be omitted or simplified in order to avoid obscuring the invention. When referring specifically to the drawings, it is emphasized that the specifics shown are illustrative and intended solely for illustrative purposes, and are presented to provide what is considered to be the most useful and easily understandable description of the principles and conceptual aspects of the invention. In this regard, no attempt has been made to provide structural details of the invention in more detail than necessary for a basic understanding of the invention, and the description provided in conjunction with the drawings will reveal to those skilled in the art how some forms of the invention may actually be carried out.

[0024] Before describing in detail at least one embodiment of the present invention, it should be understood that the present invention is not limited in its application to the configuration details and arrangement of components described below or shown in the drawings. The present invention is applicable to other embodiments which may be carried or performed in various ways, and to combinations of the disclosed embodiments. It should also be understood that the expressions and terms used herein are for illustrative purposes only and should not be considered limiting.

[0025] Some embodiments of the present invention provide efficient and economical methods and mechanisms for generating and separating materials, thereby providing improvements to the field of material separation, particularly the generation of radionuclides. In particular, methods and systems for the periodic enrichment of rare earth elements and isotopes are provided. Using a tube or ampoule having optionally one crucible or two coaxially opposing crucibles in fluid communication, a source material is held in a vacuum, and this source material is irradiated to enrich the source material with respect to the product material. Source material (e.g., 176 Irradiating with a metal Yb-enriched with respect to Yb to produce a product (for example, 177 After obtaining Lu), the mixture is sublimated to remove most of the source material, and the product material may be concentrated by, for example, heating the bottom of the tube and removing the heat from the top (cooling) to condense the sublimated source material at the top of the tube. Subsequently, the concentrated product material may be purified, while the solidified source structure may be reused in an irradiation / sublimation cycle to further enrich and concentrate the product material.

[0026] Figures 1A and 1B are high-level schematic block diagrams of an enrichment system 100 in operation according to some embodiments of the present invention. Figures 2A-2C are high-level flowcharts showing a periodic enrichment method 200 according to some embodiments of the present invention. The method steps may be performed with respect to the above system 100, which may be optionally configured to carry out method 200. In some embodiments, method 200 is 176 From Yb 177This may also include periodically generating and separating Lu, and Figure 3 shows a periodic method according to some embodiments of the present invention. 177 This is a high-level schematic, non-limiting example of the operation of enrichment system 100 for the generation and separation of Lu. However, the disclosed system 100 and method 200 may also be applied to separate other elements and / or isotopes, as disclosed herein. The elements in Figures 1A to 7C may be combined in any operational combination, and the fact that certain elements are shown in certain figures and not in others is for illustrative purposes only and not limiting.

[0027] The enrichment system 100 may include a sealing unit 150 configured to heat a tube 110 (e.g., a quartz ampoule in Figure 3) to create a vacuum inside the tube 110, and subsequently seal the tube 110, the tube 110 including a first crucible 120A having source material, which is coaxially opposed to a second crucible 120B and in fluid communication (face-to-face, with an opening that allows for the flow of material between the crucibles), the two crucibles 120A and 120B being set inside the tube 110 as schematically shown in the inset of Figure 1A, and the two crucibles 120A and 120B and the tube 110 being permeable to neutrons. The crucibles 120A and 120B may be mounted in a way that allows them to seal each other (but are shown slightly separated in Figure 1A simply for clarity), and may be coaxially aligned by an alignment device 125 (shown in a very schematic manner). In some embodiments, the alignment device 125 may include an O-ring of an inert metal. In certain embodiments, the tube 110 may not include crucibles 120A and 120B, as schematically shown in Figure 1B, and may have source material and product material deposited and sublimated on the inner surface of the tube 110. After sublimation, the tube 110 is divided into two parts, namely the remaining concentrated 177 Part 110A having Lu and sublimated 176 The portion 110B containing Yb may be separated, and the remaining concentrated 177 Lu can then be post-processed, and sublimated. 176Yb may then be reused. In some embodiments, the tube 110 may include only one crucible 120A or 120B for each material to be deposited and / or collected, as schematically shown in Figure 5B.

[0028] In response to this, as shown in Figure 2A, Method 200 may include the steps of setting up a first crucible containing a source material in fluid communication with a second crucible, coaxially opposite each other, such that both crucibles are set up inside a tube and both crucibles and the tube are permeable to neutrons (Step 210), and optionally, aligning these crucibles coaxially (Step 215). Method 200 may further include the steps of heating the tube to create a vacuum inside the tube and then sealing the tube (Step 220). For example, the source material is 176 Including Yb (for example, less than 1%) 174 (Having a Yb fraction) is also acceptable, and method 200 is as disclosed herein, 177 The method may also include periodically generating and separating Lu. Alternatively, as shown in Figure 2B, the method 200 may include optionally depositing source material in a crucible at the bottom of the tube (step 212), heating the tube to create a vacuum inside the tube and subsequently sealing the tube (step 220), and periodically generating and separating product material.

[0029] In various embodiments, the source material may be deposited in a first section 110A of a sealed tube 110 (e.g., the bottom section, optionally including a crucible 120A), from which the concentrated product material is collected, and the sublimated source material is collected in a second section 110B of the sealed tube 110 (e.g., the upper section, optionally including a crucible 120B). If two crucibles 120A, 120B are used, they are arranged coaxially with fluid communication through their opposing open ends. The tube 110 and, if used, the crucibles 120A, 120B are made from materials that are chemically inert to the respective source material and sublimated material, for example, the crucibles are made from niobium or an alloy thereof, and the tube is made from quartz or aluminum or an alloy thereof. The handling unit 180 may be configured to separate sections 110A, 110B of the tube 110 and / or crucibles 120A, 120B, if used, by various means. For example, as shown in Figures 1A, 1B, 5B, and 6, the handling unit 180 may be configured to cut the tube 110 into two parts, for example, by forming a circular groove in the sealed tube and then rupturing the tube along the groove, in order to separate the concentrated product material from the sublimated source material.

[0030] It should be noted that the terms “top” and “bottom” are used herein in a relative but non-limiting sense with respect to the opposing crucibles or other parts of the disclosed system and tube, for the sake of simplicity of explanation. In practice, as will be experimentally verified, the tube 110 may be set up and handled in any orientation (e.g., vertical, horizontal, oblique, or any other position including inversion of the parts referred to herein as “top” and “bottom”), and the sublimation process may be carried out using the sealed tube 110 in any orientation (e.g., positioned vertically, horizontally, or at some intermediate angle), and the sublimated material passes from one crucible to the opposite crucible, or from one end of the tube to the opposite end of the tube, regardless of their spatial orientation.

[0031] Crucibles 120A and 120B and / or tube 110 (for example, if no crucibles are used or only one is used) may be made from refractory materials for high-temperature processing. For example, crucibles 120A and 120B (or optionally tube 110) may be made from niobium and / or a niobium alloy further containing up to 50 mass% in total of at least one of zirconium, tungsten, tantalum, titanium, nickel, combinations thereof and / or alloys. Crucibles 120A and 120B may have a height (or length) of 3 mm to 100 mm (for example, within the range of 3 to 100 mm, 3 to 30 mm, or 30 to 100 mm), or 10 mm to 50 mm (for example, 10 mm, 20 mm, 25 mm, 30 mm, 40 mm, 50 mm, or an intermediate value), a diameter of 4 mm to 30 mm (for example, 4 mm, 6 mm, 8 mm, 10 mm, 15 mm, 20 mm, 30 mm, or an intermediate value), and a maximum thickness of 2 mm. The thickness of the side walls of crucibles 120A and 120B may be less than 0.2 mm, or within the range of 0.2 to 0.5 mm, 0.5 to 1 mm, 1 to 2 mm, or an intermediate value. Crucibles 120A and 120B may be manufactured with an inner crucible width to crucible wall thickness ratio in the range of 1:1 to 20:1, preferably 5:1, in order to provide heat transfer perpendicular to the axis of the target.

[0032] The alignment device 125 may be installed between crucibles 120A and 120B and may include one or more inner and / or outer rings, or any other components configured to ensure tight coaxial orientation of crucibles 120A and 120B relative to each other during the sealing, irradiation, and sublimation processes. The gap between crucibles 120A and 120B may be minimal or nonexistent. The joint (fit) of crucibles 120A and 120B inside the tube 110 may be configured, for example, not to be perfectly tight, in order to prevent damage to the tube 110 due to thermal expansion of crucibles 120A and 120B or other mechanical or thermal strains applied during the process.

[0033] The tube 110 may be made of quartz and may be mountable to a vacuum device 152 and then sealed when separated from the vacuum device 152 to maintain an internal vacuum. For example, the tube 110 may be welded or otherwise sealed at one end and welded or bonded at the opposite end to a quartz tube of the vacuum device 152 ( schematically shown as a vacuum connection 151), which may include a flange joint 151A (see Figures 3 and 4, with or without additional sealing 151) containing a quartz tube designed to connect to the unwelded end of the quartz tube 110, for example, using a clamping sealing device, using adhesive, or by implementing other connecting means.

[0034] For example, the tube 110 may be heated to, for example, 300°C to 600°C to desorb gas from the surface of its components, up to a maximum of 10 -7 Vacuum may be applied to reach a residual pressure in the tube down to hPa. In certain embodiments, the sealed tube 110 may be heated by the sublimation unit 170 to 400°C to 1000°C at the bottom holding the source material and to 20°C to 300°C at the top holding the sublimated material. The volume of the sealed tube 110 may be up to 100 ml, 30 ml, 10 ml, or 3 ml, or any intermediate value. The pressure inside the sealed tube 110 may be less than 100 kPa (1 bar), or between 1 and 100 kPa, 10 -2 ~1kPa, 10 -4 ~10 -2 kPa, 10 -6 ~10 -4 kPa or 10 -8 ~10 -6 kPa, or within a partial range or intermediate value. Following the creation of a vacuum in the tube 110, the tube 110 may be sealed and separated from the vacuum device 152, the seal 153 is illustrated in a very schematic manner. For example, the tube 110 may be subjected to, for example, a static vacuum (e.g., 10 -7The tubes may be welded or bonded by welding in a hydrogen flame using a non-injector single-flame burner at a pressure up to hPa, or by other means such as an acetylene lamp (torch) or laser welding. During welding for sealing, the tube 110 may be consistently heated to a temperature of 1100°C or higher (for example, if the tube 110 is made of quartz, 1100°C is close to the melting point of quartz) under constant rotation of the burner tip around the tube 110, for example. To ensure consistent heating, the flame preferably enters the wall of the tube 110 at a 90° angle, and in non-limiting examples, the burner may be positioned to produce a triangular seal 153 as schematically shown in Figure 3 by moving the burner tip around the tube 110 along a zigzag trajectory (up and down the tip of the tube 110, schematically illustrated and indicated by the number 153A). After the formation of a constriction on the tube 110 (e.g., the illustrated triangular seal 153 of the quartz ampoule), the flame intensity may increase with simultaneous extension of the lower part of the tube 110. Flame output control may be performed in both manual and automatic modes. The vacuum airtightness of the tube 110 may be verified by immersing the sealed ampoule in a container containing water and rejecting the ampoule if any trace amount of water is found inside. The ytterbium-containing tube 110 may be further placed in a container made of aluminum, steel, or a zirconium alloy to ensure mechanical strength.

[0035] The enrichment system 100 uses a source material (for example,) in a first crucible 120A inside a sealed tube 110. 176 A metal Yb enriched with Yb is irradiated with neutrons, and the source material is converted into a product material (for example, 177 The method may further include an irradiation unit 160 configured to enrich with respect to Lu. Correspondingly, as shown in Figure 2A, the method 200 includes a step (step 230) of irradiating the source material in a first crucible in a sealed tube with neutrons to enrich the source material with respect to the product material therein, for example, in a first crucible in a sealed tube 176 Yb is irradiated with neutrons, 177Enriched in relation to Lu 176 The method may include a step of generating Yb. Alternatively, as shown in Figure 2B, the method 200 may include a step (step 230A) of irradiating the source material at the bottom of a sealed tube (or in the corresponding crucible) with neutrons to enrich the source material with respect to the product material therein.

[0036] Figure 4 is a high-level schematic diagram of possible configurations and operating principles of a sealing unit 150 in the process of sealing a tube 110 according to some embodiments of the present invention. In Figure 4, tube 300 represents an unrestricted embodiment of tube 110, and crucible 301 represents unrestricted embodiments of crucibles 120A and 120B.

[0037] The tube 300, having a crucible 301 inside, may be fixed within a vacuum airtight pipe compression fitting 302 (as an indefinite example of an embodiment of the vacuum connection and / or sealing 151). The fitting 302 may be connected to a vacuum rotary feedthrough 303 having, for example, an electric actuator motor, configured to rotate the fitting 302 and the tube 300, for example, at a constant speed. The rotary feedthrough 303 may be in a fixed position and positioned using a stand 304 (which may be adjustable). The vacuum pump 305 (as an indefinite example of an embodiment of the vacuum apparatus 152) may optionally include a turbomolecular pump having a dry (oil-less) mechanical (forevacuum) pump via a bellows tube 306 to which it is connected. The vacuum pump 305 may pump up to 10 -7It may be configured to generate a vacuum of hPa. For example, a working gas may be supplied from a gas supply unit 308 to a gas torch 307 (e.g., an oxygen-hydrogen torch) configured to generate a flame temperature of at least 1500°C (2700°F). In some embodiments, the gas torch 307 may be configured to generate a flame temperature of up to 2800°C (5100°F), or an intermediate value. In some embodiments, the gas torch 307 may be replaced with a high-power laser. For example, a tube holder 309 having a weight of up to 1 / 2 pound (approximately 230 g) may be clamped (fastened) to the bottom of the tube to introduce mechanical tension into the tube. After the tube 300 has been pumped out, the tube 300 may be heated by the gas torch 307 at a position 310 above the upper crucible while being rotated by a rotating feedthrough 303 to form a seal 153, for example. The tubing material may be selected to become malleable under the heat of the torch 307 and collapse by atmospheric pressure into an airtight seal 153 on the upper crucible to form a sealed tubing shown as tubing 400 in Figure 5A described below (see also sealed tubing 110 in Figures 1A and 1B).

[0038] Figure 5A is a high-level schematic diagram of possible embodiments of a sublimation unit 170 during the sublimation process of ytterbium as an example of a source material, according to some embodiments of the present invention. The irradiated sealed tube 400 may be placed in a heat-resistant holder 401 to allow heating of the lower part of the sealed tube 400 by an electric heater 402. In some embodiments, a heat absorber 403 may be placed on top of the sealed tube 400. In some embodiments, the heat absorber 403 may also be fabricated in the form of a metal radiator / tube holder. In some embodiments, a low-temperature gas circulation 405 (e.g., at ambient temperature) from a fan or nozzle 404 may be introduced to cover the upper part of the sealed tube 400 and the heat absorber 403 (if present).

[0039] Figure 5B provides a high-level schematic diagram of a sealed tube 400 and the sublimation process within it according to several embodiments of the present invention. Figure 5B provides non-limiting examples of the sublimation process, which are also described, for example, in Figures 1A-3. In Figure 5B, sealed tubes 406, 411, and 415 represent non-limiting embodiments of tube 110, and crucibles 412, 416, and 418 represent non-limiting embodiments of crucibles 120A and 120B. Ytterbium source materials 408, 413, and 417 provide non-limiting examples of source materials, respectively, and product materials 410, 414, and 419 provide non-limiting examples of product materials, respectively. Note that Figure 5B schematically illustrates embodiments in which the bottom and / or top of tube 110 are used for deposited and / or sublimated material, replacing the use of one or both crucibles at their respective positions within the tube.

[0040] Column A schematically shows an embodiment of a compact sealed tube 406 under vacuum 407, where a fragment of ytterbium metal source material 408 is deposited, pushed in, or poured in liquid form and solidified inside the tube (left). After the sublimation process is carried out in the sublimation unit 170 (right), the ytterbium is deposited at the unheated (upper) end of the sealed tube 406. The concentrated product material 410 remains at the hot end (bottom) of the sealed tube 406. Column B schematically shows an embodiment of a compact sealed tube 411 under vacuum having a crucible 412 containing ytterbium source material 413 inside (left). After the sublimation process is carried out in the sublimation unit 170 (right), ytterbium 413 is deposited in the unheated (upper) end of the sealed tube 411, while the concentrated product material 414 remains inside the crucible 412 at the hot end (bottom) of the sealed tube. Column C schematically shows an embodiment using a compact sealed tube 415 under vacuum, having an empty crucible 418 and a crucible 416 containing the ytterbium source material 417 (left). After the sublimation process is carried out in the sublimation unit 170 (right), ytterbium 417 is deposited in the crucible 418 at the unheated (upper) end of the sealed tube 415, while the concentrated product material 419 remains inside the crucible 416 at the hot end (bottom) of the sealed tube.

[0041] Figure 6 is a high-level schematic diagram of possible configurations and operating principles of a handling unit 180 during the process of breaking a sealed tube 502 according to some embodiments of the present invention. In Figure 6, the sealed tube 502 represents a non-limiting embodiment of the tube 110.

[0042] In some embodiments, the handling unit 180 may include a pipe holder 500 having, for example, a cylindrical pit 501 for supporting the sealed pipe 502 to a depth of, for example, about half the length of the sealed pipe 502. A pipe 503 having a hinge 504 may be positioned above the cylindrical pit 501, for example coaxially therewith. In some embodiments, the hinge 504 may be replaced by a single elastic pipe. The sealed pipe 502 may be placed in the pit 501, and then a mechanical force from an electric, pneumatic, or manually moved pusher 505 may be applied to the pipe 503 until the sealed pipe 502 is broken. In some embodiments, a circular notch or groove 506 may be fabricated on the sealed pipe 502 using a glass cutting tool prior to the placement of the sealed pipe 502 into the pit 501 in order to act as an intended break point.

[0043] Disclosed herein 176 Since Yb ​​is irradiated 177 Figures 7A and 7C show non-specific examples of Lu production, with the radioactive nuclides schematically represented in Figure 7A. 177 Lu decay scheme, for different values ​​of neutron flux density, schematically shown in Figure 7B. 176 Yb irradiation time 177 The yield dependence of Lu, and the starting isotope mixture, schematically shown in Figure 7C. 174 Irradiation with different percentages of Yb and as a function of the duration of post-reactor storage / processing 177 Background information, including the specific activity of Lu, is provided. Further consideration of these properties is provided below.

[0044] The irradiation unit 160 may include the reactor core as a neutron source for neutron irradiation. The irradiation time is 177 The desired activity of Lu and the parameters of a particular reactor (neutron flux on the target) may be determined accordingly.

[0045] In some embodiments, the irradiation unit 160 may include any fusion-based source, such as a device (e.g., a nuclear reactor or generator) that carries out a deuterium-tritium or deuterium-deuterium fusion reaction and generates neutrons in a vacuum tube or chamber.

[0046] In some embodiments, the irradiation unit 160 may include any type of particle accelerator-based neutron source, in which an accelerated beam of protons or deuterons is directed into a converter or target containing beryllium, lithium, or other light nuclei, such that a neutron flux is generated when the beams collide.

[0047] In some embodiments, the irradiation unit 160 may further include a relaxation medium in the neutron path to the irradiated sealed tube, reducing the energy of the relaxed (slowed) neutrons to thermal energy (less than 0.5 eV) or resonance energy (less than 10 keV). In some embodiments, the relaxation medium may include, for example, polyethylene, carbon, beryllium, or heavy water.

[0048] The enrichment system 100 contains a source material (for example, 176 With respect to Yb, the enriched metal Yb is sublimated from the first crucible 120A to the second crucible 120B (where the source material condenses and changes from gas to solid), and the product material (for example,) is sublimated in the first crucible 120A. 177 The method may further include a sublimation unit 170 configured to concentrate Lu. Correspondingly, as shown in Figure 2B, the method 200 includes a step (step 240) of sublimating the source material from a first crucible to a second crucible and concentrating the product material in the first crucible in a sealed tube, for example, 176 Yb is sublimated from the first crucible to the second crucible, and in the first crucible 177The method may include a step of concentrating Lu in a sealed tube. Alternatively, as shown in Figure 2B, the method 200 may include a step (step 240A) of concentrating the product material in a sealed tube by sublimating the source material from the bottom (or corresponding crucible) of the sealed tube to the top (or corresponding crucible) of the sealed tube.

[0049] For example, sublimation may be carried out by heating the first crucible 120A and condensing the sublimated Yb at the bottom opposite the opening of the second crucible 120B. The heating of the first crucible 120A may be carried out to a temperature between 400°C and 1000°C (e.g., any of 400°C, 500°C, 600°C, 700°C, 800°C, 900°C, 1000°C, or an intermediate value), the temperature of the second crucible 120B may be maintained between 20°C and 300°C (e.g., any of 20°C, 40°C, 50°C, 70°C, 100°C, 200°C, 300°C, or an intermediate value), and the sublimation may be carried out for 10 minutes to 10 hours (e.g., any of 10 minutes, 30 minutes, 60 minutes, 2 hours, 4 hours, 6 hours, 10 hours, or an intermediate value). In various embodiments, heating may be carried out gradually, and / or any of the disclosed temperatures may be changed during the process to optimize the resulting yield and / or other process parameters.

[0050] The temperature difference between crucibles 120A and 120B may be achieved by heating the former and cooling the latter, and / or by using partitions to achieve at least partial heat separation of the top and bottom of the tube 110, for example by controlling different heat transfers and / or electromagnetic induction and / or high-frequency heating in the oven, by blowing air at one or more temperatures, and by providing a heat shield and / or reflector.

[0051] In various embodiments, the sublimated in the second crucible 120B 176 Yb may contain at least 97% by weight, 98% by weight, 99% by weight, 99.5% by weight, or any intermediate or higher value, in the concentrated form in the first crucible.177 Lu is initially set in the first crucible 120A at a maximum of 3% by weight, 2% by weight, 1% by weight, 0.5% by weight, or any intermediate or lower value. 176 It contains Yb. Thus, the ytterbium obtained in the sublimation process can be used to generate a new target without additional processing, and the lutetium content in the total mass in the lower crucible may reach 50% (1:1 Yb / Lu ratio) as an example, which greatly facilitates the extraction and chromatographic post-treatment processes disclosed herein.

[0052] In various embodiments, sublimation may be further used or applied to purify the source material from non-volatile impurities. In various embodiments, the enrichment system 100 may be further configured to prepare the source material by heating and sublimation (which may be repeated). For example, the disclosed process may be performed once or more times without the steps of irradiation and product extraction, and the source material may be purified once or repeatedly before formation (by irradiation) and extraction of product material from the source material. For example, the sublimation unit 170 may be further configured such that, for example, the source material is deposited in a first section 110A and / or a first crucible 120A of a sealed tube 110 (from which the source material is sublimated into a second section 110B and / or a second crucible 120B of the sealed tube 110) and the source material is sublimated in preparation for irradiation so that a purified source material is formed, which is then used as a source material to be irradiated to enrich a target material and sublimated to concentrate a product material, while non-volatile impurities remain in the first section 110A and / or the first crucible 120A of the sealed tube 110. Correspondingly, the handling unit 180 may be configured to break the tube 110 after the source material has been purified by sublimation, separate the purified source material from the broken tube (and optionally from the first crucible), and use the purified source material as the source material for continuous enrichment by irradiation and sublimation as disclosed herein. Correspondingly, the sealing unit 150 may be configured to seal the tube 110 having the purified source material for continuous enrichment by irradiation and sublimation as disclosed herein.

[0053] Non-volatile impurities that may be completely or partially removed from the source material include lanthanum (La), gadolinium (Gd), lutetium (Lu) (during previous irradiation). 174 It may be present due to the presence of Yb impurities. 175 Yb 175 (including Lu decay products), hafnium (Hf), erbium (Er), thulium (Tm) (during previous irradiation) 168It may be present due to the presence of Yb impurities. 169 Yb 169 Examples include Tm decay products. As schematically shown in Figure 2C, Method 200 includes the steps of: optionally depositing source material in a crucible at the bottom of the tube (Step 212A); heating the tube to create a vacuum inside the tube and then sealing the tube (Step 220A); sublimating the material from the bottom of the sealed tube (or the corresponding crucible) to the top of the sealed tube (or the corresponding crucible inside it) to concentrate the source material or product material inside the sealed tube (Step 240B); and optionally breaking the seal of the tube and removing the bottom of the sealed tube (or the crucible inside it) containing non-volatile impurities. The process may include a step of separating the sublimated material from the top (or crucible inside) of a sealed tube (step 250B), and optionally a step of purifying the source material and / or product material from non-volatile impurities (step 205), by repeating method steps 212A, 220A, 240B, 250B (depositing 212A, heating 220A, sublimating 240B, and breaking 250B) over multiple cycles using the sublimated material from the top of the tube from each cycle to provide material to the bottom of the tube for the next cycle (step 260B).

[0054] The enrichment system 100 breaks the seal 153 of the tube and concentrates the product material (for example, 177 A first crucible 120A containing Lu is used to sublimate a source material (for example, 176 The method may further include a handling unit 180 configured to separate the second crucible 120B having the source material (metal Yb enriched with respect to Yb) from the second crucible 120B having the sublimated source material, and to use the second crucible 120B having the source material for a continuous enrichment cycle through system 100 (as schematically shown). Correspondingly, as shown in Figure 2A, the method 200 includes a step (step 250) of breaking the seal of the tube and separating the first crucible having the enriched product material from the second crucible having the sublimated source material, for example, breaking the seal of the tube and enriching 177The process may include the steps of separating a first crucible containing Lu from a second crucible containing sublimated Yb, and repeating steps 210-250 (setting 210, heating 220, irradiation 230, sublimation 240, and breaking 250) over multiple cycles (step 260), for example, using the second crucible containing sublimated source material from each cycle as the first crucible containing source material for the next cycle material (see schematic diagram in Figure 1A, located at the top of the diagram of the handling unit 180). Alternatively, as shown in Figure 2B, Method 200 includes a step (step 250A) of breaking the seal of the tube and separating the bottom of the sealed tube (or the crucible inside it) having the concentrated product material from the top of the sealed tube (or the crucible inside it) having the sublimated source material, for example, breaking the seal of the tube and the concentrated 177 The method may include the steps of separating the bottom tube portion having Lu from the upper tube portion having sublimated Yb, and repeating method steps 212-250A (depositing 212, heating 220, irradiation 230A, sublimation 240A, and breaking 250A) over multiple cycles (step 260A), for example, using the upper tube portion having sublimated Yb from each cycle as the deposit at the bottom of the tube having Yb for the next cycle (see schematic diagram in Figure 1B, located at the top of the diagram of the handling unit 180).

[0055] It should be noted that the tube may be broken in a specific environment, for example, in an inert atmosphere of a noble gas (e.g., Ar, He, Ne, Kr, Xe) or other inert gas, or in a partial vacuum. Accordingly, in some embodiments, the step 250 of breaking the sealed tube can be performed in an inert atmosphere.

[0056] Typically, less than 1% by weight of the source material is converted into the product material, and the remaining source material (after sublimating from the first crucible 120A and solidifying on the second crucible 120B) may be used as the source material in the next cycle of the process, optionally without additional processing. The second crucible 120B having the condensed source material is removed from the tube 110 and used as the first crucible 120A in a new tube 110 used in consecutive cycles of the disclosed system 100 and method 200, and the entire process (steps 210 / 212, 215, 220) of hermetically connecting the quartz tube and the ampoule of the vacuum system as described above may be repeated. This is an important advantage of the disclosed target processing method that there is no additional step of transferring expensive isotope-enriched ytterbium that could lead to material loss or contamination.

[0057] Enrichment system 100 may further include a post-treatment unit 190 configured to obtain a purified product material (e.g., 177 Lu) from the concentrated product material from a plurality of enrichment cycles. Correspondingly, method 200 may include a step (step 270) of post-treating the concentrated product material from a plurality of repetitions to obtain a purified product material, e.g., post-treating the concentrated 177 Lu from a plurality of cycles to obtain purified 177 Lu.

[0058] The post-treatment may be used to remove impurities of the non-volatile ytterbium compound. For example, the post-treatment may be performed on the concentrated 177 Lu in the first crucible 120A (or tube portion) (the remaining 176The process may include dissolving the compound (containing Yb) in hydrochloric acid and / or nitric acid (or a combination or mixture thereof), and purifying it by chromatography. Additionally or complementaryly, organophosphoric acids, particularly di-(2-ethylhexyl)-orthophosphoric acid (DEHPA or HDEHP) (structural formula 1), 2-ethylhexyl-2-ethylhexylphosphonic acid (HEH[EHP]) (structural formula 2) (e.g., available under the brand names LN resin and LN2 resin) (Triskem®) may be used, in some cases, after separation in hydrochloric acid solution and / or extraction chromatography in an insoluble hydrophilic aliphatic polymer (e.g., acrylic ether). [ka]

[0059] In certain embodiments, post-processing may be implemented as multi-step separation and purification (for example, due to large differences in the amounts of ytterbium and lutetium). In non-limiting examples, post-processing may include (i) separation of large amounts of ytterbium, (ii) 177 The separation may be carried out in at least three steps: (iii) primary isolation of Lu, and (iii) secondary (final) purification of the product. In all three steps, the separation may be carried out on an LN2 resin. The acidity differs significantly in the inter-step transitions, including the desorption of lutetium (with ytterbium) from the column in the previous step and its sorption on the column in the later step. The simplest way to remove the acid is to evaporate the solution. However, this is a time-consuming operation, and this operation can be replaced by sorption using a TODGA (or DGA) resin as an adsorbent. This resin contains tetraoctyldiglycolamide (structural formula 3) and can sorb REE (rare earth elements) from strongly acidic solutions and weakly retains REE in dilute acidic solutions. [ka]

[0060] In an unrestricted experimental setting, in this process 177The yield of Lu reaches 73%, and the total purification coefficient from ytterbium exceeds 10 6 and is sufficient for the production of 177 Lu for pharmaceutical purposes. The total processing time is about 4 hours, which is also a good indicator. When using a combination of two steps of sublimation and chromatography, 177 the extraction of Lu can reach up to 90%, and the mass of the processed ytterbium target can increase up to several grams.

[0061] In various embodiments, the post-treatment yield may exceed 50%, 60%, 70%, 80% or intermediate values (for extracting product materials such as 177 Lu from the concentrated product material), and the total purification coefficient of method 200 may be at least one million (10 6 ), increasing the concentration of product materials such as 177 Lu in the final product relative to the initial material.

[0062] In certain embodiments, system 100 and / or method 200 may be applied to source materials and product materials having very different boiling points, for example, having boiling points that differ by at least 10%, 20%, 30%, 40%, 50%, intermediate values, or more (in °K) for metals and / or isotopes. In non-limiting examples, the source material may be zinc, the product material may be copper, or the source material may be europium, and the product material may be terbium.

[0063] Advantageously, certain embodiments provide for the efficient production of lutetium-177 ( 177 Lu), which is one of the most promising radionuclides for cancer treatment due to its unique radiochemical properties and the possibility of chemical bonding with organic molecules. The disclosed embodiments overcome various prior art difficulties in the production of this isotope. 177 Lu, as schematically shown in FIG. 7A, has a half-life T 177 1 / 2 ​It is a radioactive isotope with a decay time of 6.646 days, and decays with the emission of medium-energy beta and gamma rays. 177 Lu is lutetium-176( 176 Lu) or Ytterbium-176( 176 It can be obtained by irradiation of starting materials with reactor neutrons, which can be used as isotopes of Yb, but what is far larger and more practically interesting is 176 By Yb irradiation 177 This is the generation of Lu. 176 Yb irradiation targets the only isotope of lutetium. 177 This leads to the formation of Lu. Therefore, this method makes it possible to obtain a product with a specific activity equivalent to the theoretical value, i.e., 110 kCi / g. 177 Lu yield (departure) 176 The dependence of Yb on Ci per gram is shown in Figure 7B. The dependence does not have a clear maximum value within a practically significant range of irradiation cycle duration. This means that the irradiation time or the mass of the starting radionuclide can be selected according to a given performance. Even in high-neutron flux reactors, the burning of the starting material is very low. 177 Lu accumulation intermediate product, 177 Yb, with its relatively short half-life (T 1 / 2 The exposure time (1.91 hours) allows for the reuse of the starting material after exposure for the decay of this radionuclide over several days. However, the actual activity (or radioactivity) of the irradiated material (and therefore the required duration of exposure) is determined by the decay of other impurity isotopes. In any case, the ability to reuse the starting material multiple times is extremely important, given the high cost of isotope-enriched materials.

[0064] Equally important is the isotopic composition of the starting material. 177 The calculation of the yield and specific activity of Lu is performed using the starting material. 176 This was based on the assumption of a 100% Yb content. However, in reality, ytterbium-176 oxide supplied by enrichment facilities contains up to 2-3% isotopes. 174It may contain Yb in the starting composition. 174 The presence of the Yb isotope is 175 Yb(T 1 / 2 This results in an accumulation of 4.18 days, 175 Yb after the end of irradiation 175 It decayed into Lu, and therefore accumulated during irradiation. 177 This reduces the specific activity of Lu. The effect of insufficient enrichment of the starting material is shown in Figure 7C. 177 The calculation of the specific activity of Lu is given for a model irradiation schedule at the SM-3 reactor (Research Institute of Atomic Reactors, Dimitrovgrad, Russia), taking into account the actual duration of the reactor cycle, the time required to extract the irradiated targets from the reactor and deliver them to the processing site, and the actual radiochemical processing. 174 If the Yb content exceeds 1%, during irradiation and subsequent post-reactor operation... 177 The specific activity of Lu changes dramatically, and the "direct" method (isotopes enriched) 176 (generated by irradiation with Lu) 177 It decreases to the value of the specific activity of Lu. In other words, in the starting material 174 The presence of Yb isotope impurities can, in prior art, lead to the formation of quasi-standard products. This necessitates the use of starting materials with the highest possible enrichment levels, however, this is less than 0.2%. 174 Since materials containing the Yb fraction are commercially available, this does not currently pose a major problem. Through repeated use (recycling) of the starting materials, 174 It is also worth noting that the Yb content decreases due to burnout, and that, for example, each continuous irradiation cycle improves the quality of the starting material.

[0065] Depending on the irradiation conditions, the generation within the target 177The amount of Lu varies between 0.05 and 0.3% (by weight). Assuming that the amount of ytterbium in the final product should not exceed 5% of the mass of lutetium (otherwise the yield of the usable fraction during the synthesis of the labeled compound will decrease proportionally), the separation coefficient of these two elements is at least n × 10⁻⁶. 6 It should be so. The electron shell structures of ytterbium and lutetium are extremely similar (the outer electron shell configuration is 4f, respectively). 14 6s 2 and 4f 14 5d 1 6s 2 Therefore, separating these two elements is an extremely difficult chemical task because their chemical properties are very similar.

[0066] When separating ytterbium and lutetium in their +3 oxidation state, the separation is typically characterized by a low separation factor. This often leads to the need for multiple iterations of the separation process, particularly due to the chromatographic design of the process. This approach is used for separation by extraction (extraction chromatography) or ion exchange (ion exchange chromatography).

[0067] The boiling points of metallic lutetium and metallic ytterbium are 3395°C and 1196°C, respectively. This characteristic can be used to separate lutetium and ytterbium. At high temperatures (above 400°C), the saturated vapor pressure of elemental metallic ytterbium significantly exceeds that of elemental lutetium, which essentially enables their separation. However, this method is not yet widely used due to the technical complexity of remote handling of radioactive materials within a radiation-shielded chamber. The separation must be carried out under vacuum conditions at temperatures above 400°C, and the materials of the apparatus must be inert to ytterbium vapor.

[0068] The following provides non-limiting experimental examples for performing the disclosed procedure. (More than 99% ytterbium-176 isotope) 1760.5 g of ytterbium metal enriched with Yb) was placed in the first niobium crucible. The first crucible containing the ytterbium and the empty second crucible were placed coaxially inside a quartz tube sealed at one end. This quartz tube was then connected to a sealing unit by its open end, and the sealing unit was filled into the quartz tube by applying a vacuum pump. -2 A vacuum of less than kPa was generated. Heating and sealing of the tubes were performed using a hydrogen-oxygen torch in the sealing unit. The sealed tubes were then placed in an aluminum overpack and positioned in an irradiation channel in the reactor core, where they were irradiated for 150 minutes. The overpack was then removed from the reactor, and the sealed tubes were removed from the aluminum overpack. Lutetium-177( 177 Lu) and Ytterbium-175( 175 The amount of Yb was measured by their activity using gamma spectroscopy, and the amount of lutetium-177 inside the tube was measured. 177 The generation of Lu was confirmed. Next, the sealed tube was delivered to the laboratory in a shielded container and placed in a sublimation unit, where the end of the sealed tube having the first crucible was heated by the induced current generated by the radio frequency (RF) coil of the sublimation unit. 176 To control the accumulation of Yb, air at a controlled temperature was supplied to its end in the tube. Based on the glow of the first crucible, its temperature during the process was 400°C to 1000°C over the 60 minutes the sublimation process was carried out. After sublimation, the sealed tube was ruptured in an argon bath, and the first and second crucibles were removed from the ruptured tube. The sublimated and accumulated ytterbium material (more than 99% of the original mass) was collected in the second crucible, which was later sealed in a new tube as a new first crucible, and the irradiation and sublimation process was repeated to obtain more 177 Lu was produced. The residue in the first crucible was washed with 3M nitric acid and measured by gamma spectroscopy, and lutetium was used as the product material. 177 The presence and amount of lutetium (Lu) were confirmed. The amount of lutetium observed in the solution was found to be more than 90% of the amount calculated to be present in the sealed tube at the start of sublimation.

[0069] Advantageously, compared to prior art such as International Publication No. 2021102167, which uses a movable cold finger to collect Yb vapor, the disclosed embodiments overcome the drawbacks of the prior art, including (i) requiring a large-capacity reactor, which results in a large amount of residual gas that can form non-volatile compounds with the ytterbium metal and hinder the evaporation of the metal; (ii) the lack of an obvious simple method to collect the ytterbium collected on the cold finger and return it to the sublimation cycle; and (iii) due to the small surface area of ​​the cold finger on which the ytterbium vapor condenses, some of the vapor may transform into a fine dispersion form, which is flammable and can explode upon contact with air.

[0070] Advantageously, the disclosed embodiments overcome the shortcomings of the prior art. For example, prior art such as U.S. Patent Application Publication No. 20240011125, which uses a vacuum chamber having multiple feedthroughs and connections, has the following drawbacks compared to the disclosed embodiments of the present invention: For example, the teachings of U.S. Patent Application Publication No. 20240011125 require (i) sealing and pumping the vacuum chamber before the start of the sublimation process, which is time-consuming, during which the lutetium-177 product material is partially lost due to radioactive decay; (ii) a dedicated, undisclosed process to collect the ytterbium separated after each sublimation, which is obscure and complex, as well as introducing further material (ytterbium); and (iii) a dedicated pelletizing process for the ytterbium, which requires additional effort and time to produce a homogeneous target, and in some cases involves further material loss. All of these problems are not required and / or solved by the disclosed embodiments of the present invention, as described above.

[0071] Advantageously, the disclosed embodiments increase the useful yield of the lutetium-177 radionuclide (increase the extraction of the radionuclide from the product material) by carrying out the direct (no intermediate steps) and highly efficient (yield exceeding 90 mass%) recovery of the enriched ytterbium material of the treated target. The disclosed embodiments also enable the separation of other metals and / or isotopes having very different boiling points, such as zinc and copper, europium and terbium.

[0072] In the above description, "one embodiment" refers to an example or embodiment of the present invention. The various appearances of "one embodiment," "one embodiment," "a particular embodiment," or "several embodiments" do not necessarily all refer to the same embodiment. Various features of the present invention may be described in the context of a single embodiment, but those features may be provided separately or in any suitable combination. Conversely, the present invention may be described herein in the context of a separate embodiment for clarity, but the present invention may be implemented in a single embodiment. A particular embodiment of the present invention may include features from different embodiments disclosed above, and a particular embodiment may incorporate elements from other embodiments disclosed above. The disclosure of elements of the present invention in the context of a particular embodiment is not intended to limit their use to that particular embodiment only. Furthermore, it should be understood that the present invention can be carried out or implemented in a variety of ways, and that the present invention can be implemented in specific embodiments other than those outlined in the above description.

[0073] The present invention is not limited to those figures or corresponding descriptions. For example, the flow does not need to move through each box or state illustrated, nor does it need to move in the exact same order as illustrated and described. Unless otherwise defined, the meanings of technical and scientific terms used herein are to be generally understood by those skilled in the art to which the present invention pertains. Although the present invention has been described in relation to a limited number of embodiments, these should not be construed as limiting the scope of the invention, but rather as illustrating some preferred embodiments. Other possible modifications, variations, and applications are also within the scope of the invention. Accordingly, the scope of the present invention should not be limited by what has been described herein, but should be limited by the appended claims and their legal equivalents.

Claims

1. It is an enrichment system, A sealing unit configured to heat a tube to create a vacuum inside the tube and then seal the tube, wherein the tube is permeable to neutrons, heat resistant up to at least 600°C, and includes a source material, An irradiation unit configured to irradiate the source material inside the sealed tube with neutrons to enrich the source material with respect to the product material therein, A sublimation unit configured to sublimate a source material in a sealed tube and concentrate the product material in the sealed tube, A handling unit configured to break the seal of the tube, separate the concentrated product material from the sublimated source material, and use the sublimated source material as a source material for a continuous enrichment cycle through the system. An enrichment system that includes this.

2. The enrichment system according to claim 1, wherein the source material is deposited in a first section of the sealed tube, the concentrated product material is collected therefrom, and the sublimated source material is collected in a second section of the sealed tube.

3. The enrichment system according to claim 2, wherein at least one of the first and second sections includes a corresponding crucible that is chemically inert to the respective source material and sublimated material.

4. The enrichment system according to claim 3, wherein neither of the first and second sections includes a crucible, or one of the first and second sections includes a crucible, and the handling unit is further configured to form a circular groove in the sealed tube and subsequently break the tube along the groove to separate the concentrated product material from the sublimated source material.

5. The enrichment system according to claim 3, wherein both the first and second sections include corresponding crucibles arranged coaxially and in fluid communication through opposing open ends.

6. The enrichment system according to claim 5, wherein the crucible is made of niobium or an alloy thereof, and the tube is made of quartz, niobium or an alloy thereof, or aluminum or an alloy thereof.

7. The enrichment system according to claim 5, wherein the thickness of the side wall of the crucible is less than 0.2 mm, or within the range of 0.2 to 0.5 mm, 0.5 to 1 mm, or 1 to 2 mm.

8. The enrichment system according to claim 5, wherein the height of the crucible is within the range of 3 to 100 mm, 3 to 30 mm, or 30 to 100 mm.

9. The enrichment system according to any one of claims 1 to 8, wherein the volume of the tube is a maximum of 100 ml, 30 ml, 10 ml, or 3 ml.

10. The pressure inside the sealed tube is less than 100 kPa (1 bar), or between 1 and 100 kPa. －２ ~1 kPa, 10 －４ ~10 －２ kPa, 10 －６ ~10 －４ kPa or 10 －８ ~10 －６ An enrichment system according to any one of claims 1 to 9, wherein the pressure is within any range of kPa.

11. The source material is an isotope １７６ containing ytterbium enriched to more than 90 wt% with respect to Yb, and the product material １７７ contains Lu, and the enrichment system according to any one of claims 1 to 10.

12. The enrichment system according to any one of claims 1 to 11, further comprising a post-processing unit configured to obtain a purified product material from the concentrated product material from a plurality of enrichment cycles.

13. The post-processing unit is concentrated １７７ Dissolve Lu in hydrochloric acid and / or nitric acid, １７７ The enrichment system according to claim 12, configured to purify Lu by chromatography.

14. The enrichment system according to claim 12, wherein the yield of the post-processing unit exceeds 60%, and the total purification coefficient is at least 1 million.

15. The sublimation unit uses the source material １７６ Sublimate at least 99% by weight of Yb, １７６ The concentrated Yb contains at most 1% by weight. １７７ The enrichment system according to any one of claims 1 to 14, further configured so as not to leave any residue in Lu.

16. The enrichment system according to any one of claims 1 to 15, further comprising a heater configured to heat the source material to 400°C to 1000°C, and a heat absorber configured to maintain the sublimation section of the tube at 20°C to 300°C.

17. The enrichment system according to any one of claims 1 to 16, wherein the sublimation unit and the handling unit are further configured to purify the source material before irradiation by sublimating the source material in the sealed tube, removing any remaining non-volatile impurities, and using the purified source material for irradiation.

18. Using the enrichment system described in claim 1 １７７ A method for producing Lu, The sealed inside of the tube １７６ The Yb source material is irradiated with neutrons, and the source material １７７ A process for enriching the Lu product material, From the irradiated source material １７６ Yb is sublimated in the sealed tube. １７７ A process for concentrating the Lu product material, Sublimated １７６ Irradiation using Yb as a source material and from the irradiated source material １７６ By repeatedly sublimating Yb, the above １７７ A process to further concentrate the Lu product material and Methods that include...

19. concentrated the above １７７ The method according to claim 18, further comprising a step of post-processing the Lu product material.

20. The method according to claim 18 or claim 19, wherein the irradiation and sublimation are carried out in the sealed tube without a crucible.

21. The method according to any one of claims 18 to 20, wherein the irradiation and sublimation are performed on the source material in the crucible within the sealed tube.

22. Sublimated １７６ The method according to any one of claims 18 to 21, further comprising the step of collecting Yb into another crucible.

23. The method according to any one of claims 18 to 22, further comprising the step of purifying the source material from non-volatile impurities before the irradiation.

24. １７６ Yb １７７ A system for converting to Lu, A sealed tube under vacuum, Including a first open end, inside １７６ A first crucible containing the Yb source material and positioned within the sealed tube, A second crucible, which includes a second open end and is disposed within the sealed tube, is coaxially aligned with the first crucible and in fluid communication with it, and the second open end is positioned opposite the first open end of the first crucible. The sealed pipe １７６ Irradiate the Yb source material with neutrons, １７７ An irradiation unit configured to produce Lu-product material and A system comprising the tube and both crucibles, wherein the tube and both crucibles are made of a material that is transparent (permeable) to neutrons.

25. The crucible is made of niobium and / or a niobium alloy further containing at least one of zirconium, tungsten, tantalum, titanium, nickel, combinations thereof, and / or alloys in total up to 50% by weight. The crucible has a length of 10 to 50 mm, a diameter of 4 to 30 mm, and a maximum thickness of 2 mm. The aforementioned tube is made from quartz. The system according to claim 24.

26. １７６ From Yb source ingredients １７７ A method for preparing a Lu product material, wherein the material is prepared in a sealed tube under vacuum. １７６ The Yb source material is irradiated with neutrons, １７６ Sublimating the Yb source material as described above １７７ Process for producing Lu product material The sealed tube includes a first open end and contains the １７６ A method comprising a first crucible containing a Yb source material and a second crucible having a second open end and positioned within the sealed tube, wherein the first and second crucibles are coaxially aligned and in fluid communication within the sealed tube, with the second open end of the second crucible facing the first open end of the first crucible, and the tube and both crucibles are made of a neutron-transparent (permeable) material.

27. Break the sealed tube, １７７ The first crucible containing Lu was sublimated. １７６ A step of separating Yb from the second crucible, For subsequent cycles １７６ Sublimation from each cycle to prepare the first crucible containing Yb １７６ A step of repeating the method over a plurality of cycles using the second crucible having Yb, Concentrated from multiple cycles １７７ Lu is purified, １７７ The process of obtaining the Lu product and The method according to claim 26, further comprising:

28. The crucible is made of niobium and / or a niobium alloy further containing at least one of zirconium, tungsten, tantalum, titanium, nickel, combinations thereof, and / or alloys in total up to 50% by weight. The crucible has a length of 10 to 50 mm, a diameter of 4 to 30 mm, and a maximum thickness of 2 mm. The aforementioned tube is made from quartz. The method according to claim 27.

29. The sublimation is performed by heating the first crucible and sublimating the １７６ The method according to claim 27 or claim 28, wherein Yb is condensed at the bottom of the second crucible opposite the second open end of the second crucible.

30. The method according to claim 29, further comprising the steps of heating the first crucible to 400°C to 1000°C and maintaining the temperature of the second crucible at 20°C to 300°C, wherein the sublimation is carried out for 10 minutes to 10 hours.

31. Sublimated in the second crucible １７６ Yb is initially set in the first crucible. １７６ Containing at least 99% by weight of Yb, concentrated in the first crucible １７７ Lu is initially set in the first crucible. １７６ The method according to any one of claims 26 to 30, wherein the Yb content is at most 1% by weight.

32. Purification is carried out in the first crucible. １７７ The method according to any one of claims 26 to 31, comprising dissolving Lu in hydrochloric acid and / or nitric acid, and purifying it by chromatography.

33. The method according to any one of claims 26 to 32, wherein the purification yield is greater than 60% and the total purification factor is at least 1 million.

34. Sublimated in the second crucible １７６ Yb was initially in the first crucible. １７６ Containing at least 99% by weight of Yb, concentrated in the first crucible １７７ Lu is initially set in the first crucible. １７６ The method according to any one of claims 26 to 33, wherein the Yb content is at most 1% by weight.

35. Before the irradiation １７６ The method according to any one of claims 26 to 34, further comprising the step of purifying the Yb source material from non-volatile impurities.

36. periodic １７７ A method for generating and separating Lu, １７６ A step of setting up a first crucible containing Yb in fluid communication with a second crucible, coaxially opposite each other, wherein both crucibles are set up inside a tube, and both crucibles and the tube are transparent (permeable) to neutrons, The process involves heating the tube to create a vacuum inside the tube, and then sealing the tube. In the sealed tube, in the first crucible １７６ Irradiate Yb with neutrons, １７７ Enriched with respect to Lu １７６ The process of generating Yb, １７６ Yb is sublimated from the first crucible to the second crucible, and the contents of the first crucible １７７ A step of concentrating Lu in the sealed tube, The seal of the aforementioned tube is broken, and the concentrated １７７ The first crucible containing Lu was sublimated. １７６ A step of separating Yb from the second crucible, Next cycle １７６ Sublimation from each cycle to prepare the first crucible containing Yb １７６ A process of repeating the setting, heating, irradiation, sublimation and breaking process multiple times using the second crucible having Yb, Concentrated from multiple cycles １７７ Lu is post-processed and purified １７７ The process of obtaining Lu and Methods that include...

37. The crucible is made of niobium and / or a niobium alloy further containing at least one of zirconium, tungsten, tantalum, titanium, nickel, combinations thereof, and / or alloys in total up to 50% by weight. The crucible has a length of 10 to 50 mm, a diameter of 4 to 30 mm, and a maximum thickness of 2 mm. The tube is made of quartz, is attachable to a vacuum device, and is then sealed when separated from the vacuum device to maintain an internal vacuum. The method according to claim 36.

38. The method according to claim 36 or claim 37, further comprising coaxially aligning the first crucible and the second crucible.

39. The sublimation is performed by heating the first crucible and sublimating the １７６ The method according to any one of claims 36 to 38, wherein Yb is condensed at the bottom of the second crucible opposite the opening of the second crucible.

40. The method according to claim 39, wherein the first crucible is heated to 400°C to 1000°C, the temperature of the second crucible is maintained at 20°C to 300°C, and the sublimation is carried out for 10 minutes to 10 hours.

41. Sublimated in the second crucible １７６ Yb is initially set in the first crucible. １７６ Containing at least 99% by weight of Yb, concentrated in the first crucible １７７ Lu is initially set in the first crucible. １７６ The method according to any one of claims 36 to 40, wherein the Yb content is at most 1% by weight.

42. The post-treatment is performed on the concentrated in the first crucible. １７７ The method according to any one of claims 36 to 41, comprising dissolving Lu in hydrochloric acid and / or nitric acid, and purifying it by chromatography.

43. The method according to any one of claims 36 to 42, wherein the yield of the post-treatment exceeds 60%, and the total purification coefficient of the method is at least 1 million.

44. Before the irradiation １７６ The method according to any one of claims 36 to 43, further comprising the step of purifying the Yb source material from non-volatile impurities.

45. A periodic enrichment method, A step of setting up a first crucible containing a source material, coaxially opposite a second crucible, and in fluid communication with it, wherein both crucibles are set up inside a tube, and both crucibles and the tube are transparent (permeable) to neutrons, The process involves heating the tube to create a vacuum inside the tube, and then sealing the tube. A step of irradiating the source material in the first crucible inside the sealed tube with neutrons to enrich the source material with respect to the product material therein, A step of sublimating the source material from the first crucible to the second crucible, and concentrating the product material in the first crucible in the sealed tube, A step of breaking the seal of the tube and separating the first crucible containing the concentrated product material from the second crucible containing the sublimated source material, A step of repeating the setting, heating, irradiating, sublimating and breaking process multiple times using the second crucible containing the sublimated source material from each cycle in order to prepare the first crucible containing the source material for the next cycle, A step of post-processing the concentrated product material from the plurality of cycles to obtain a purified product material. A periodic enrichment method including [a specific term].

46. The aforementioned source material is １７６ The product material contains Yb, and the product material is １７７ A periodic enrichment method according to claim 45, comprising Lu.

47. The periodic enrichment method according to claim 45 or claim 46, wherein the source material and the product material have boiling points that differ by at least 20%.

48. The periodic enrichment method according to claim 47, wherein the source material is zinc and the product material is copper, or the source material is europium and the product material is terbium.

49. It is an enrichment system, A sealing unit configured to heat a tube to create a vacuum inside the tube and then seal the tube, wherein the tube includes a first crucible having a source material that is in fluid communication with a second crucible coaxially opposite it, both crucibles are set inside the tube, and both crucibles and the tube are transparent (permeable) to neutrons, An irradiation unit configured to irradiate the source material in the first crucible inside the sealed tube with neutrons to enrich the source material with respect to the product material therein, A sublimation unit configured to sublimate a source material from the first crucible to the second crucible, and to concentrate the product material in the first crucible within the sealed tube, A handling unit configured to break the seal of the tube, separate the first crucible containing the concentrated product material from the second crucible containing the sublimated source material, and use the second crucible containing the sublimated source material as the first crucible containing the source material for a continuous enrichment cycle through the system, A post-processing unit configured to obtain purified product material from the concentrated product material from multiple enrichment cycles, An enrichment system that includes this.

50. The crucible is made of niobium and / or a niobium alloy further containing at least one of zirconium, tungsten, tantalum, titanium, nickel, combinations thereof, and / or alloys in total up to 50% by weight. The crucible has a length of 10 to 50 mm, a diameter of 4 to 30 mm, and a maximum thickness of 2 mm. The tube is made of quartz, is attachable to a vacuum device, and is then sealed when separated from the vacuum device to maintain an internal vacuum. The system according to claim 49.

51. The system according to claim 49 or 50, wherein the tube further includes an alignment device configured to maintain the first crucible and the second crucible in a coaxially aligned state.

52. The sublimation unit heats the first crucible and sublimes the １７６ The system according to any one of claims 49 to 51, configured to condense Yb at the bottom of the second crucible opposite the opening of the second crucible.

53. The system according to claim 52, wherein the first crucible is heated to 400°C to 1000°C, the temperature of the second crucible is maintained at 20°C to 300°C, and the sublimation is carried out for 10 minutes to 10 hours.

54. Sublimated in the second crucible １７６ Yb is initially set in the first crucible. １７６ Containing at least 99% by weight of Yb, concentrated in the first crucible １７７ Lu is initially set in the first crucible. １７６ The system according to any one of claims 49 to 53, which contains at most 1% by weight of Yb.

55. The post-processing unit processes the concentrated in the first crucible. １７７ Dissolve Lu in hydrochloric acid and / or nitric acid, １７７ The system according to any one of claims 49 to 54, configured to purify Lu by chromatography.

56. The system according to any one of claims 49 to 55, wherein the yield of the post-processing unit exceeds 60%, and the total purification coefficient is at least 1 million.

57. The system according to any one of claims 49 to 56, wherein the sublimation unit and the handling unit are further configured to purify the source material before irradiation by sublimating the source material in the sealed tube, removing any remaining non-volatile impurities, and using the purified source material for irradiation.

58. The system according to claim 57, wherein the non-volatile impurity includes at least one of lanthanum (La), gadolinium (Gd), erbium (Er), thulium (Tm) containing decay products of ytterbium-169, hafnium (Hf), and / or lutetium (Lu) containing decay products of ytterbium-175.

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