Separation of rare earth elements in low partial pressure environments of oxygen-containing gases

Abstract

A method for purifying lutetium includes sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium over a sublimation / distillation time in an environment at a temperature ranging from 400 DEG C to 2000 DEG C to leave a lutetium composition comprising a higher weight percent of lutetium than present in the solid composition. Wherein the environment contains water vapor, and the water vapor is present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation time.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 404,080, filed on September 6, 2022, which is incorporated herein by reference in its entirety. Technical Field

[0003] This disclosure generally relates to the separation and purification of rare earth elements. More specifically, this disclosure relates to the separation and purification of lutetium from irradiated targets that include other rare earth metals such as ytterbium. Background Art

[0004] Lutetium - 177 (Lu - 177) is a radioactive isotope used in the treatment of neuroendocrine tumors, prostate cancer, breast cancer, kidney cancer, pancreatic cancer, and other cancers. In the coming years, approximately 70,000 patients per year will require treatment with Lu - 177.

[0005] Accordingly, there is a need for improved techniques for separating and purifying radioactive isotopes such as Lu - 177. Summary of the Invention

[0006] According to a first aspect of the present disclosure, a method for purifying lutetium includes: sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment having a temperature range of 400 °C to 2000 °C over a sublimation / distillation time to leave a lutetium composition, the lutetium composition comprising a higher weight percentage of lutetium than was present in the solid composition, wherein the environment comprises water vapor and the water vapor is present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation time.

[0007] A second aspect includes the method of the first aspect, wherein the water vapor is present in the environment at a partial pressure of 1.5 torr or less during at least 50% of the sublimation / distillation time.

[0008] A third aspect includes the method of the first or second aspect, wherein the water vapor is present in the environment at a partial pressure of 1.5 torr or less during at least 75% of the sublimation / distillation time.

[0009] A fourth aspect includes the method of any of the foregoing aspects, wherein the water vapor is present in the environment at a partial pressure of 1.5 torr or less during at least 95% of the sublimation / distillation time.

[0010] A fifth aspect includes the method of any of the foregoing aspects, wherein the water vapor is present in the environment at a partial pressure of 1.5 torr or less during the entire sublimation / distillation time.

[0011] A sixth aspect includes the method of any of the foregoing aspects, wherein the water vapor is present in the environment at a partial pressure of 1 torr or less.

[0012] The seventh aspect includes the method of any of the foregoing aspects, wherein water vapor is present in the environment at a partial pressure of 0.1 torr or lower.

[0013] The eighth aspect includes the method of any of the foregoing aspects, wherein the environment includes O2 gas, and the O2 gas is present in the environment at a partial pressure of 1 torr or lower.

[0014] The ninth aspect includes the method of the eighth aspect, wherein the O2 gas is present in the environment at a partial pressure of 0.1 torr or lower.

[0015] The tenth aspect includes the method of the eighth or ninth aspect, wherein the O2 gas is present in the environment at a partial pressure of 0.01 torr or lower.

[0016] The eleventh aspect includes the method of any of the foregoing aspects, wherein the environment includes CO2 gas, and the CO2 gas is present in the environment at a partial pressure of 1 torr or lower.

[0017] The twelfth aspect includes the method of the eleventh aspect, wherein the CO2 gas is present in the environment at a partial pressure of 0.1 torr or lower.

[0018] The thirteenth aspect includes the method of the eleventh or twelfth aspect, wherein the CO2 gas is present in the environment at a partial pressure of 0.01 torr or lower.

[0019] The fourteenth aspect includes the method of any of the foregoing aspects, wherein the environment includes NO2 gas, and the NO2 gas is present in the environment at a partial pressure of 1 torr or lower.

[0020] The fifteenth aspect includes the method of the fourteenth aspect, wherein the NO2 gas is present in the environment at a partial pressure of 0.1 torr or lower.

[0021] The sixteenth aspect includes the method of the fourteenth or fifteenth aspect, wherein the NO2 gas is present in the environment at a partial pressure of 0.01 torr or lower.

[0022] The seventeenth aspect includes the method of any of the foregoing aspects, wherein the environment includes CO gas, and the CO gas is present in the environment at a partial pressure of 1 torr or lower.

[0023] The eighteenth aspect includes the method of the seventeenth aspect, wherein the CO gas is present in the environment at a partial pressure of 0.1 torr or lower.

[0024] The nineteenth aspect includes the method of the seventeenth or eighteenth aspect, wherein the CO gas is present in the environment at a partial pressure of 0.01 torr or lower.

[0025] The twentieth aspect includes the method of any of the foregoing aspects, wherein the solid composition is contained in a crucible of a sublimation / distillation system, and sublimating or distilling from the solid composition includes heating the crucible such that ytterbium sublimates, distills, or both sublimates and distills from the solid composition and is collected on a collection surface of the sublimation / distillation system.

[0026] The twenty - first aspect includes the method of the twentieth aspect, wherein the sublimation / distillation system further includes a residual gas analyzer configured to detect one or more gases present in the environment.

[0027] The twenty - second aspect includes the method of the twenty - first aspect, wherein the method further includes: detecting H2 gas with the residual gas analyzer while sublimating or distilling ytterbium from the solid composition; and reducing the temperature in the environment to 90 °C or lower after detecting that the H2 gas is at or below a threshold level.

[0028] The twenty - third aspect includes the method of the twenty - second aspect, wherein the threshold level includes 0.1 ppm of H2.

[0029] The twenty - fourth aspect includes the method of any of the foregoing aspects, and the method further includes collecting ytterbium for reuse.

[0030] The twenty - fifth aspect includes the method of any of the foregoing aspects, wherein the environment includes a reduced - pressure environment, and the reduced - pressure environment includes a reduced pressure in the range of 1 x 10 -8 torr to 700 torr.

[0031] The twenty - sixth aspect includes the method of any of the twenty - fifth aspects, wherein the reduced pressure is 1 x 10 -3 or lower.

[0032] The twenty - seventh aspect includes the method of any of the foregoing aspects, wherein the temperature is in the range of 450 °C to 1500 °C.

[0033] The twenty - eighth aspect includes the method of any of the foregoing aspects, wherein the temperature is lower than 700 °C.

[0034] The twenty - ninth aspect includes the method of any of the foregoing aspects, and the method further includes chromatographically separating a lutetium composition to further enrich lutetium in the lutetium composition.

[0035] The thirtieth aspect includes the method of the twenty - ninth aspect, and further includes: dissolving the lutetium composition in an acid to form a dissolved lutetium solution, adding a chelating agent to the dissolved lutetium solution and neutralizing with a base to form a chelated lutetium solution containing both chelated lutetium and ytterbium, chromatographically separating the chelated lutetium solution, collecting a purified chelated lutetium fraction, and de - chelating the lutetium to obtain purified lutetium.

[0036] The thirty - first aspect includes the method of the thirtieth aspect, wherein the lutetium purity of the purified chelated lutetium fraction is higher than the lutetium purity in the dissolved lutetium solution.

[0037] The thirty - second aspect includes the method of the thirtieth or thirty - first aspect, wherein the de - chelation includes contacting the purified chelated lutetium fraction with an acid, which is hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, persulfuric acid, perchloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, or a mixture of two or more thereof.

[0038] According to a thirty - third aspect of the present invention, a method for purifying lutetium includes: sublimating or distilling ytterbium from a solid composition containing ytterbium and lutetium in an environment with a temperature range of 400 °C to 2000 °C over a sublimation / distillation time to leave a lutetium composition, the lutetium composition containing a higher weight percentage of lutetium than present in the solid composition, wherein the environment contains one or more oxygen - containing gases, and the one or more oxygen - containing gases are present in the environment at a total pressure of 10 torr or less during the sublimation / distillation time.

[0039] The thirty - fourth aspect includes the method of the thirty - third aspect, wherein the one or more oxygen - containing gases contain a total pressure of 10 torr or less in the environment for at least 50% of the sublimation / distillation time.

[0040] The thirty - fifth aspect includes the method of the thirty - third or thirty - fourth aspect, wherein the one or more oxygen - containing gases contain a total pressure of 10 torr or less in the environment for at least 75% of the sublimation / distillation time.

[0041] The thirty - sixth aspect includes the method of any one of the thirty - third to thirty - fifth aspects, wherein the one or more oxygen - containing gases contain a total pressure of 10 torr or less in the environment for at least 95% of the sublimation / distillation time. The thirty - seventh aspect includes the method of any one of the thirty - third to thirty - sixth aspects, wherein the one or more oxygen - containing gases contain a total pressure of 10 torr or less in the environment throughout the sublimation / distillation time.

[0042] The thirty - eighth aspect includes the method of any one of the thirty - third to thirty - seventh aspects, wherein the total pressure of the one or more oxygen - containing gases present in the environment is 0.01 torr or less.

[0043] The thirty - ninth aspect includes the method of any one of the thirty - third to thirty - eighth aspects, wherein the total pressure of the one or more oxygen - containing gases present in the environment is 0.001 torr or less.

[0044] The fortieth aspect includes the method of any one of the thirty-third to thirty-ninth aspects, wherein one or more oxygen-containing gases present in the environment include one or more of water vapor, O2 gas, CO2 gas, NO2 gas, CO gas, hydrocarbon gas, and alcohol gas.

[0045] The forty-first aspect includes the method of any one of the thirty-third to fortieth aspects, wherein the total pressure in the environment is 10 torr or greater during the sublimation / distillation time.

[0046] The forty-second aspect includes the method of any one of the thirty-third to forty-first aspects, wherein one or more oxygen-containing gases are present in the environment at a total partial pressure in the range of 0.01 torr to 10 torr during the sublimation / distillation time.

[0047] According to the forty-third aspect of the present disclosure, in an environment with a temperature range of 400 °C to 2000 °C, ytterbium is sublimated or distilled from a solid composition containing ytterbium and lutetium through a sublimation / distillation time to leave a lutetium composition, and the lutetium composition contains a higher weight percentage of lutetium than that present in the solid composition. Wherein the environment contains one or more oxygen-containing gases, and one or more oxygen-containing gases are present in the environment at a total partial pressure of 1 torr or less during the sublimation / distillation time. Wherein one of the one or more oxygen-containing gases contains water vapor, and the water vapor is present in the environment at a partial pressure of 0.1 torr or less during the sublimation / distillation time, and wherein the total pressure in the environment is 1 torr or greater during the sublimation / distillation time.

[0048] The forty-fourth aspect includes the method of the forty-third aspect, wherein the method further includes: detecting H2 gas with a residual gas analyzer while sublimating or distilling ytterbium from the solid composition; and reducing the temperature in the environment to 90 °C or lower after detecting that the H2 gas reaches or is below a threshold level.

[0049] The forty-fifth aspect includes the method of the forty-third or forty-fourth aspect, wherein one or more oxygen-containing gases are present in the environment at a total partial pressure in the range of 0.01 torr to 10 torr during the sublimation / distillation time.

[0050] The forty-sixth aspect includes the method of any of the foregoing aspects, wherein the solid composition ranges from 0.5 g to 10 g at the start during the sublimation / distillation time.

[0051] The forty-seventh aspect includes the method of any of the foregoing aspects, wherein the water vapor is present in the environment at a partial pressure of 0.001 torr to 1.5 torr during the sublimation / distillation time.

[0052] These features and additional features provided by the embodiments described herein will be more fully understood in connection with the following detailed description and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] The embodiments set forth in the drawings are illustrative and exemplary in nature and are not intended to limit the subject matter defined by the claims. The following detailed description of illustrative embodiments can be understood when read in conjunction with the following drawings, in which like structures are represented by like reference numerals, wherein:

[0054] Figure 1 is a T-x-y diagram of lutetium and ytterbium at a constant pressure of 1 μtorr; and

[0055] Figure 2 schematically shows a chamber for distillation / sublimation of ytterbium and lutetium according to one or more embodiments shown and described herein. DETAILED DESCRIPTION

[0056] Generally referring to the drawings, embodiments of the present disclosure relate to methods for separating rare earth elements using sublimation or distillation processes in a high-temperature environment having a low partial pressure of certain gases, such as oxygen-containing gases that react with the rare earth elements. For example, embodiments of the present disclosure relate to separating lutetium from a composition (e.g., a solid composition) containing ytterbium and lutetium to obtain high-purity lutetium, such as high-purity lutetium isotopes, such as Lu-177. Lu-177 is useful in many medical applications because it emits low-energy β particles during decay that are suitable for treating tumors. Lu-177 also emits two γ rays that can be used in diagnostic tests. Isotopes having both therapeutic and diagnostic properties are referred to as "theranostic" isotopes. Lu-177 is not only theranostic, it also has a half-life of 6.65 days, which allows for more complex chemical reactions and easy global distribution. Lu-177 also exhibits chemical properties that allow it to bind to a variety of biomolecules and can be used in various medical treatments.

[0057] There are mainly two production routes for producing lutetium-177. One is through the neutron capture reaction on Lu-176; Lu-176(n,γ)Lu-177. This production method is called carrier-added (ca) Lu-177. The carrier is the same element (Lu-176 in this case) or an isotope of a similar element having the same chemical form as the isotope of interest. In trace chemistry, due to the extremely low concentration of the chemical element or isotope of interest, its chemical properties do not behave as expected. In addition, isotopes of the same element cannot be separated by chemical methods and mass separation techniques need to be employed. Therefore, the carrier method results in the production of Lu-177 being limited in medical applications.

[0058] A second production method of Lu-177 is to perform a neutron capture reaction on ytterbium-176 (Yb-176) (Yb-176(n,γ)Yb-177) to generate Yb-177. Then, Yb-177 rapidly (half-life of 1.911 hours) decays to Lu-177 via β decay. Yb-174 impurities are usually present in Yb-176, resulting in the presence of Lu-175 impurities in the final product. This process is considered a "carrier-free addition" process. This process can be carried out in the form of ytterbium metal or ytterbium oxide.

[0059] The present disclosure describes a separation process for obtaining Yb and Lu from a carrier-free addition process. The process includes a distillation / sublimation process to purify lutetium and remove excess ytterbium after irradiation. The process can also include further purifying lutetium using a chromatographic separation process. Since the amount of material that can be processed at any one time in the chromatographic separation process is limited, the process of enriching lutetium before chromatographic separation allows the recovery scale of the product lutetium to reach a higher level than before. For example, the current chromatographic separation process itself is limited to a target material of 20 mg each time, and the processing time for each time is 30 min to 1 h. Combining distillation / sublimation and chromatographic separation allows the use of a larger target material, and the product is separated by distillation and then the separated product is transferred to the chromatographic process. Processing a 20 g sample using only chromatography would require 1,000 batches of processing and would result in a large amount of material loss.

[0060] The separation of Yb and Lu can at least partially utilize the difference in their vapor pressures at specific temperatures and pressures. For example, at standard temperature and pressure, the boiling point of Yb is 1196 °C, while the boiling point of Lu is 3402 °C. The vapor pressure difference at specific temperatures and pressures can be used to separate Yb and Lu by sublimation and / or distillation. Now refer to Figure 1 , graph 50 is a T-x-y diagram of lutetium and ytterbium at a constant pressure of 1 μtorr. In Figure 1 , line 54 represents the composition of the condensed phase (i.e., the bubble point) at a given temperature, while line 52 represents the vapor phase (i.e., the dew point). Graph 50 is drawn using the assumptions of ideal gas and ideal solution, which are valid under low pressure, high temperature, and the similar chemical properties of the two components.

[0061] In the sublimation process, the solid phase of the element is directly converted to the gas phase by heating, and then the gas phase can be collected for later use. In the distillation process, the solid is heated to its boiling point (passing through the liquid phase) and evaporated. After the vapor condenses, the vaporized fraction can be recovered downstream. In this case, ytterbium is evaporated (and can be collected downstream for later use), leaving behind a lutetium-rich material. This can be carried out on a large scale, thereby increasing the amount of available lutetium. It is worth noting that the collected ytterbium can be recycled back to the reactor to produce more lutetium in subsequent runs of the process.

[0062] Now refer to Figure 2 FIG. , which schematically shows a sublimation / distillation apparatus 100 for separating rare earth elements such as lutetium and ytterbium. The sublimation / distillation apparatus 100 includes a chamber 105 having gas, cooling, vacuum, power, and instrument feedthroughs. The sublimation / distillation apparatus 100 is capable of creating an environment with multiple conditions in the chamber 105, such as high temperature, low pressure, high concentration of inert gas, and low partial pressure of a selected gas. The sublimation / distillation apparatus 100 includes a crucible 190 and a heating element 170, which can be accommodated together in the chamber 105. The chamber 105 may also include a sealable access port 110 that provides the user with selective access to the crucible 190, e.g., to contact and transfer the sample contained in the crucible 190. The crucible 190 may be made of a refractory material (e.g., molybdenum or tantalum). In some embodiments, the heating element 170 is an induction heating element, such as an RF induction coil. The crucible 190 may be suspended or supported within the RF induction heating coil. A temperature sensor 180 monitors the temperature of the crucible 190, and a pressure sensing instrument 140 monitors the total pressure in the chamber 105 and the partial pressure of one or more gases of interest, such as oxygen-containing gas. In some embodiments, the pressure sensing instrument 140 includes a residual gas analyzer configured to detect one or more gases present in the environment, e.g., the partial pressure of one or more gases present in the environment. The sublimation / distillation apparatus 100 also includes a vacuum pump interface 150 and at least one port 200 for introducing an inert gas.

[0063] The sublimation / distillation apparatus 100 includes a collection surface 160 that forms a cold surface. The collection surface 160 can be actively cooled by a cooling water line 130. The temperature of the collection surface 160 can be monitored by a temperature sensor 120. In some embodiments, the collection surface 160 may also include a cold finger 165 (e.g., a cooling rod) that extends from the collection surface 160 towards the crucible 190 and is disposed directly above the crucible 190. The cold finger 165 and the collection surface 160 are movable, which allows the open end of the crucible 190 to be opened to the vacuum system (e.g., to the chamber 105) or pressed and sealed onto the collection surface 160. In some embodiments, the cold finger 165 includes an end effector. In fact, the cold finger 165 can extend from the collection surface 160 towards the crucible 190 such that the cold finger 165 extends into the crucible 190 when the collection surface 160 is sealed to the crucible 190. Like the collection surface 160, the cold finger 165 can also be actively cooled. In other embodiments, the collection surface 160 can be the surface (e.g., the inner surface) of a collection crucible. The collection crucible can be a second crucible having an open end that faces the open end of the crucible 190.

[0064] Still referring to Figure 2 , a method for separating and purifying lutetium from a composition containing lutetium and ytterbium (e.g., solid composition 102) will now be described. The method includes subliming or distilling ytterbium from the solid composition 102 for a sublimation / distillation time in an environment having a low partial pressure of one or more oxygen-containing gases (e.g., H2O gas (i.e., water vapor), O2 gas, CO2 gas, CO gas, NO2 gas, hydrocarbon gases (including methane), and alcohol gases (including methanol, ethanol, and isopropyl alcohol)), and at a temperature of 400 °C to 2000 °C, to leave a lutetium composition that contains a higher weight percentage of lutetium than was present in the solid composition 102. In practice, at the start of the separation process, the solid composition 102 is contained in a crucible 190, and subliming or distilling ytterbium from the solid composition 102 includes, for example, heating the crucible 190 using a heating element 170 such that ytterbium sublimes, distills, or sublimes and distills from the solid composition 102 and is collected on a collection surface 160, including on a cold finger 165 in some embodiments and on the inner surface of a collection crucible in some embodiments. As described above, the ytterbium sublimed / distilled from the solid composition can be recovered as an additional target material for irradiation and reuse in subsequent separation processes.

[0065] The sample produced by the sublimation / distillation process (“lutetium composition”) is enriched in lutetium compared to the solid composition entering the process. The solid composition can have a mass in the range of 0.1 g to 15 g, such as 0.5 g to 10 g, 1 g to 10 g, 1 g to 5 g, 1 g to 2 g, such as 0.1 g, 0.25 g, 0.5 g, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 5 g, 5.5 g, 6 g, 6.5 g, 7 g, 8 g, 9 g, 10 g, 11 g, 12 g, 13 g, 14 g, 15 g, at the start of the sublimation / distillation process (e.g., at the start of the sublimation / distillation time). Yield and purity can be measured in a variety of ways. For example, in some embodiments, the process yields an ytterbium mass reduction of the solid composition from 1000:1 to 10000:1. In other words, after the sublimation / distillation is completed, there is 1000 to 10,000 times less ytterbium in the sample than prior to the process (i.e., than was present in the solid composition). In some embodiments, in the recovered lutetium composition (i.e., the material in the crucible that is subjected to acid dissolution), there can be 1 wt% to 90 wt% ytterbium relative to the total remaining mass, which will subsequently be separated in the chromatographic process as described below. In other embodiments, the ytterbium collected from the sublimation / distillation is collected in an amount of 90 wt% to 99.999 wt% of the ytterbium present in the solid composition. Purification steps are also carried out to remove other trace metals and contaminants. For example, materials such as metals, metal oxides, or metal ions of K, Na, Ca, Fe, Al, Si, Ni, Cu, Pb, La, Ce, Lu (non-radioactive), Eu, Sn, Er, Tm. In other words, the method includes sublimating, distilling, or a combination of both, a sample containing Yb-176 and Lu-177 to remove at least a portion of Yb-176 from the sample and form a sample enriched in Lu-177.

[0066] Purification can be achieved, as observed, to reduce Yb to less than 1 / 1000 (i.e., the amount of Yb present is reduced to 1 / 1000). This includes reducing to approximately less than 1 / 3000, less than 1 / 8000, less than 1 / 10000, with a minimum and including approximately 1 / 40000. However, higher Yb reduction may be required to meet the purity requirements of some pharmaceuticals. Therefore, additional purification can be performed prior to use in pharmaceutical applications. Such purification can be obtained by using chelating agents and / or chromatographic separation.

[0067] Furthermore, without being bound by theory, reducing the relative amount of oxygen-containing gas in the environment during sublimation / distillation time reduces the oxidation reaction between the solid composition and the oxygen-containing gas. For example, ytterbium separated from the solid composition can react with water vapor to form Yb2O3 and H2 gas, or Yb(OH)3 and H2 gas. By reducing oxidation, contaminants in the separated lutetium and ytterbium can be minimized. Oxidation can result in a higher ytterbium concentration in the lutetium composition, which subsequently requires more effort in subsequent separation steps (such as chromatographic separation) to purify the lutetium composition. Ytterbium is highly reactive and will readily react and consume oxygen species in the environment at sublimation or distillation temperatures, even reducing otherwise stable molecules or materials. Since the solid composition typically contains less than 0.1% lutetium, an increase in ytterbium oxidation can result in significant contamination of the lutetium fraction in the lutetium composition. Additionally, converting ytterbium to other non-metallic forms hinders its reuse as an irradiated metal target, thus requiring further chemical conversion to restore it to the metallic form and causing further losses.

[0068] However, it is difficult to completely remove the oxygen-containing gas from the environment. In fact, in some embodiments, the presence of a small amount of water vapor or other oxygen-containing gas in the environment is useful. The pressure sensing instrument 140 (e.g., residual gas analyzer) of the sublimation / distillation apparatus 100 is configured to detect H2 gas. Without being limited by theory, H2 gas is an exhaust gas component of the sublimation process, formed by the reaction of H2O with the ytterbium metal component in the solid composition to form an oxide of Yb or a hydroxide of Yb and H2 gas. H2 gas is detected by the pressure sensing instrument 140 (e.g., residual gas analyzer) during the sublimation / distillation process, and can be used to determine the time when the separation of lutetium and ytterbium from the solid composition is completed based on the decrease in the H2 detection signal. In some embodiments, the method includes detecting H2 gas with the pressure sensing instrument 140 (e.g., residual gas analyzer) while subliming or distilling ytterbium from the solid composition. After detecting that the H2 gas is at or below a threshold level, the temperature in the environment is reduced to a threshold temperature. Thus, the presence of oxygen-containing gas, although at a low level, is beneficial for better controlling the sublimation / distillation process. In some embodiments, the threshold temperature is 90 °C or lower, such as 85 °C or lower, 80 °C or lower, 75 °C or lower, 70 °C or lower, 65 °C or lower, 60 °C or lower, 55 °C or lower, 50 °C or lower, or any value within the range bounded by any two of these values. After reaching the threshold temperature, the separated lutetium and the separated ytterbium can be recovered for further processing (lutetium) or reuse (ytterbium). In some embodiments, the threshold level of H2 gas is in the range of 0.02 ppm to 0.5 ppm H2, such as 0.03 ppm, 0.04 ppm, 0.05 ppm, 0.06 ppm, 0.07 ppm, 0.08 ppm, 0.08 ppm, 0.09 ppm, 0.1 ppm, 0.125 ppm, 0.15 ppm, 0.175 ppm, 0.2 ppm, 0.225 ppm, 0.25 ppm, 0.275 ppm, 0.3 ppm, 0.35 ppm, 0.4 ppm, 0.45 ppm, 0.5 ppm, any range bounded by any two of these values, or any value within the range bounded by any two of these values.

[0069] In some embodiments, water vapor is present in the environment and is present at a partial pressure of 10 torr or less during sublimation / distillation, such as 5 torr or less, 2 torr or less, 1 torr or less, 0.75 torr or less, 0.5 torr or less, 0.25 torr or less, 0.1 torr or less, 0.075 torr or less, 0.05 torr or less, 0.025 torr or less, 0.02 torr or less, 0.01 torr or less, 0.0075 torr or less, 0.005 torr or less, 0.0025 torr or less, 0.002 torr or less, 0.001 torr or less, 0.00075 torr or less, 0.0005 torr or less, 0.00025 torr or less, 0.0002 torr or less, 0.0001 torr or less, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints. In other words, water vapor in the environment is present at a partial pressure within the range of greater than 0 torr to 10 torr during sublimation / distillation, such as greater than 0 torr to 5 torr, greater than 0 torr to 2 torr, greater than 0 torr to 1 torr, greater than 0 torr to 0.75 torr, greater than 0 torr to 0.5 torr, greater than 0 torr to 0.25 torr, greater than 0 torr to 0.1 torr, greater than 0 torr to 0.075 torr, greater than 0 torr to 0.05 torr, greater than 0 torr to 0.025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.0075 torr, greater than 0 torr to 0.005 torr, greater than 0 torr to 0.0025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.00075 torr, greater than 0 torr to 0.0005 torr, greater than 0 torr to 0.00025 torr, greater than 0 torr to 0.0002 torr, greater than 0 torr to 0.0001 torr, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints.Example ranges of water vapor partial pressure with a relatively high lower limit include from 0.001 torr to 10 torr, from 0.001 torr to 1.5 torr, from 0.001 torr to 1 torr, from 0.01 torr to 10 torr, from 0.01 torr to 1.5 torr, from 0.01 torr to 0.1 torr, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints.

[0070] Without being bound by theory, increasing the size of the solid composition increases the amount of water vapor tolerable in the environment. In fact, without being bound by theory, the partial pressure of water vapor can increase linearly with an increase in the mass of the solid composition while maintaining substantially the same percentage of oxidation (assuming that chamber 105 in which each of these comparative sublimations / distillations occurs has the same volume). For example, in chamber 105 having a volume of 1 cubic foot, 5% of about 1 g of the solid composition will form oxides of Yb or hydroxides of Yb and H2 gas due to oxidation at the start of the sublimation / distillation time in an environment with a water vapor partial pressure of about 0.1 torr, while 5% of about 10 g of the solid composition will form oxides of Yb or hydroxides of Yb and H2 gas due to oxidation at the start of the sublimation / distillation time in an environment with a water vapor partial pressure of about 1.1 torr. Further, without still being bound by theory, changing the volume of chamber 105 changes the amount of water vapor tolerable in the environment, where for an increasing volume of chamber 105, it may be necessary to reduce the relative partial pressure of water vapor, and for a decreasing volume of chamber 105, it may be necessary to increase the relative partial pressure of oxygen.

[0071] It is contemplated that water vapor is present within any of the above ranges and values for at least 50% of the sublimation / distillation time, such as for at least 55% of the sublimation / distillation time, for at least 60% of the sublimation / distillation time, for at least 65% of the sublimation / distillation time, for at least 70% of the sublimation / distillation time, for at least 75% of the sublimation / distillation time, for at least 80% of the sublimation / distillation time, for at least 85% of the sublimation / distillation time, for at least 90% of the sublimation / distillation time, for at least 95% of the sublimation / distillation time, for at least 96% of the sublimation / distillation time, for at least 97% of the sublimation / distillation time, for at least 98% of the sublimation / distillation time, for at least 99% of the sublimation / distillation time, or for the entire sublimation / distillation time.

[0072] In some embodiments, O2 gas is present in the environment and is present at a partial pressure of 10 torr or less during the sublimation / distillation time, such as 5 torr or less, 2 torr or less, 1 torr or less, 0.75 torr or less, 0.5 torr or less, 0.25 torr or less, 0.1 torr or less, 0.075 torr or less, 0.05 torr or less, 0.025 torr or less, 0.02 torr or less, 0.01 torr or less, 0.0075 torr or less, 0.005 torr or less, 0.0025 torr or less, 0.002 torr or less, 0.001 torr or less, 0.00075 torr or less, 0.0005 torr or less, 0.00025 torr or less, 0002 torr or less, 0.0001 torr or less, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints. In other words, O2 gas is present in the environment at a partial pressure within the range greater than 0 torr to 10 torr during the sublimation / distillation time, such as greater than 0 torr to 5 torr, greater than 0 torr to 2 torr, greater than 0 torr to 1 torr, greater than 0 torr to 0.75 torr, greater than 0 torr to 0.5 torr, greater than 0 torr to 0.25 torr, greater than 0 torr to 0.1 torr, greater than 0 torr to 0.075 torr, greater than 0 torr to 0.05 torr, greater than 0 torr to 0.025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.0075 torr, greater than 0 torr to 0.005 torr, greater than 0 torr to 0.0025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.00075 torr, greater than 0 torr to 0.0005 torr, greater than 0 torr to 0.00025 torr, greater than 0 torr to 0.0002 torr, greater than 0 torr to 0.0001 torr, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints.Exemplary ranges of the O2 gas partial pressure with a relatively high lower limit are considered, including 0.001 torr to 10 torr, 0.001 torr to 1.5 torr, 0.001 torr to 1 torr, 0.01 torr to 10 torr, 0.01 torr to 1.5 torr, 0.01 torr to 0.1 torr, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints. Additionally, it is contemplated that the O2 gas is present at any one of the above ranges and values for at least 50% of the sublimation / distillation time, such as for at least 55% of the sublimation / distillation time, for at least 60% of the sublimation / distillation time, for at least 65% of the sublimation / distillation time, for at least 70% of the sublimation / distillation time, for at least 75% of the sublimation / distillation time, for at least 80% of the sublimation / distillation time, for at least 85% of the sublimation / distillation time, for at least 90% of the sublimation / distillation time, for at least 95% of the sublimation / distillation time, for at least 96% of the sublimation / distillation time, for at least 97% of the sublimation / distillation time, for at least 98% of the sublimation / distillation time, for at least 99% of the sublimation / distillation time, or for the entire sublimation / distillation time.

[0073] In some embodiments, CO2 gas is present in the environment and has a partial pressure of 10 torr or less during sublimation / distillation, such as 5 torr or less, 2 torr or less, 1 torr or less, 0.75 torr or less, 0.5 torr or less, 0.25 or less, 0.1 torr or less, 0.075 torr or less, 0.05 torr or less, 0.025 torr or less, 0.02 torr or less, 0.01 torr or less, 0.0075 torr or less, 0.005 torr or less, 0.0025 torr or less, 0.002 torr or less, 0.001 torr or less, 0.00075 torr or less, 0.0005 torr or less, 0.00025 torr or less, 0002 torr or less, 0.0001 torr or less, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints. In other words, during sublimation / distillation, CO2 gas is present in the environment with a partial pressure in the range greater than 0 torr to 10 torr, such as greater than 0 torr to 5 torr, greater than 0 torr to 2 torr, greater than 0 torr to 1 torr, greater than 0 torr to 0.75 torr, greater than 0 torr to 0.5 torr, greater than 0 torr to 0.25 torr, greater than 0 torr to 0.1 torr, greater than 0 torr to 0.075 torr, greater than 0 torr to 0.05 torr, greater than 0 torr to 0.025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.0075 torr, greater than 0 torr to 0.005 torr, greater than 0 torr to 0.0025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.00075 torr, greater than 0 torr to 0.0005 torr, greater than 0 torr to 0.00025 torr, greater than 0 torr to 0.0002 torr, greater than 0 torr to 0.0001 torr, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints.Exemplary ranges of the partial pressure of CO2 gas with a relatively high lower limit are considered, including 0.001 torr to 10 torr, 0.001 torr to 1.5 torr, 0.001 torr to 1 torr, 0.01 torr to 10 torr, 0.01 torr to 1.5 torr, 0.01 torr to 0.1 torr, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints. Additionally, it is contemplated that the CO2 gas is present at any one of the above ranges and values for at least 50% of the sublimation / distillation time, such as for at least 55% of the sublimation / distillation time, for at least 60% of the sublimation / distillation time, for at least 65% of the sublimation / distillation time, for at least 70% of the sublimation / distillation time, for at least 75% of the sublimation / distillation time, for at least 80% of the sublimation / distillation time, for at least 85% of the sublimation / distillation time, for at least 90% of the sublimation / distillation time, for at least 95% of the sublimation / distillation time, for at least 96% of the sublimation / distillation time, for at least 97% of the sublimation / distillation time, for at least 98% of the sublimation / distillation time, for at least 99% of the sublimation / distillation time, or for the entire sublimation / distillation period.

[0074] In some embodiments, NO2 gas is present in the environment and is present at a partial pressure of 10 torr or less during sublimation / distillation, such as 5 torr or less, 2 torr or less, 1 torr or less, 0.75 torr or less, 0.5 torr or less, 0.25 torr or less, 0.1 torr or less, 0.075 torr or less, 0.05 torr or less, 0.025 torr or less, 0.02 torr or less, 0.01 torr or less, 0.0075 torr or less, 0.005 torr or less, 0.0025 torr or less, 0.002 torr or less, 0.001 torr or less, 0.00075 torr or less, 0.0005 torr or less, 0.00025 torr or less, 0002 torr or less, 0.0001 torr or less, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints. In other words, NO2 gas is present in the environment at a partial pressure within the range greater than 0 torr to 10 torr during sublimation / distillation, such as greater than 0 torr to 5 torr, greater than 0 torr to 2 torr, greater than 0 torr to 1 torr, greater than 0 torr to 0.75 torr, greater than 0 torr to 0.5 torr, greater than 0 torr to 0.25 torr, greater than 0 torr to torr0.1 torr, greater than 0 torr to 0.075 torr, greater than 0 torr to 0.05 torr, greater than 0 torr to 0.025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.0075 torr, greater than 0 torr to 0.005 torr, greater than 0 torr to 0.0025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.00075 torr, greater than 0 torr to 0.0005 torr, greater than 0 torr to 0.00025 torr, greater than 0 torr to 0.0002 torr, greater than 0 torr to 0.0001 torr, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints.Exemplary ranges of NO2 gas partial pressure with relatively high lower limits are considered, including from 0.001 torr to 10 torr, from 0.001 torr to 1.5 torr, from 0.001 torr to 1 torr, from 0.01 torr to 10 torr, from 0.01 torr to 1.5 torr, from 0.01 torr to 0.1 torr, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints. Additionally, it is contemplated that NO2 gas is present at any one of the above ranges and values for at least 50% of the sublimation / distillation time, such as for at least 55% of the sublimation / distillation time, for at least 60% of the sublimation / distillation time, for at least 65% of the sublimation / distillation time, for at least 70% of the sublimation / distillation time, for at least 75% of the sublimation / distillation time, for at least 80% of the sublimation / distillation time, for at least 85% of the sublimation / distillation time, for at least 90% of the sublimation / distillation time, for at least 95% of the sublimation / distillation time, for at least 96% of the sublimation / distillation time, for at least 97% of the sublimation / distillation time, for at least 98% of the sublimation / distillation time, for at least 99% of the sublimation / distillation time, or for the entire sublimation / distillation time.

[0075] In some embodiments, CO gas is present in the environment and has a partial pressure of 10 torr or less during the sublimation / distillation time, such as 5 torr or less, 2 torr or less, 1 torr or less, 0.75 torr or less, 0.5 torr or less, 0.25 or less, 0.1 torr or less, 0.075 torr or less, 0.05 torr or less, 0.025 torr or less, 0.02 torr or less, 0.01 torr or less, 0.0075 torr or less, 0.005 torr or less, 0.0025 torr or less, 0.002 torr or less, 0.001 torr or less, 0.00075 torr or less, 0.0005 torr or less, 0.00025 torr or less, 0002 torr or less, 0.0001 torr or less, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints. In other words, CO gas is present in the environment during the sublimation / distillation time with a partial pressure in the range greater than 0 torr to 10 torr, such as greater than 0 torr to 5 torr, greater than 0 torr to 2 torr, greater than 0 torr to 1 torr, greater than 0 torr to 0.75 torr, greater than 0 torr to 0.5 torr, greater than 0 torr to 0.25 torr, greater than 0 torr to 0.1 torr, greater than 0 torr to 0.075 torr, greater than 0 torr to 0.05 torr, greater than 0 torr to 0.025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.0075 torr, greater than 0 torr to 0.005 torr, greater than 0 torr to 0.0025 torr, greater than 0 torr to 0.002 torr, greater than 0 torr to 0.001 torr, greater than 0 torr to 0.00075 torr, greater than 0 torr to 0.0005 torr, greater than 0 torr to 0.00025 torr, greater than 0 torr to 0.0002 torr, greater than 0 torr to 0.0001 torr, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints.Exemplary ranges are contemplated that have a relatively high lower limit for the partial pressure of CO gas, including from 0.001 torr to 10 torr, from 0.001 torr to 1.5 torr, from 0.001 torr to 1 torr, from 0.01 torr to 10 torr, from 0.01 torr to 1.5 torr, from 0.01 torr to 0.1 torr, or any range that has any two of these values as endpoints, or any value within a range that has any two of these values as endpoints. Additionally, it is contemplated that the CO gas is present at any one of the foregoing ranges and values for at least 50% of the sublimation / distillation time, such as for at least 55% of the sublimation / distillation time, for at least 60% of the sublimation / distillation time, for at least 65% of the sublimation / distillation time, for at least 70% of the sublimation / distillation time, for at least 75% of the sublimation / distillation time, for at least 80% of the sublimation / distillation time, for at least 85% of the sublimation / distillation time, for at least 90% of the sublimation / distillation time, for at least 95% of the sublimation / distillation time, for at least 96% of the sublimation / distillation time, for at least 97% of the sublimation / distillation time, for at least 98% of the sublimation / distillation time, for at least 99% of the sublimation / distillation time, or for the entire sublimation / distillation time.

[0076] In some embodiments, one or more oxygen-containing gases are present in the environment and the total pressure (e.g., the sum of the partial pressures of all oxygen-containing gases in the environment) is 50 torr or less during the sublimation / distillation time, such as 40 torr or less, 30 torr or less, 25 torr or less, 15 torr or less, 10 torr or less, 7.5 torr or less, 5 torr or less, 2.5 torr or less, 2 torr or less, 1 torr or less, 0.75 torr or less, 0.5 torr or less, 0.25 torr or less, 0.2 torr or less, 0.1 torr or less, 0.075 torr or less, 0.05 torr or less, 0.025 torr or less, 0.02 torr or less, 0.01 torr or less, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints. In other words, the total pressure of one or more oxygen-containing gases present in the environment is in the range of greater than 0 torr to 50 torr during the sublimation / distillation time, such as greater than 0 torr to 40 torr, greater than 0 torr to 30 torr, greater than 0 torr to 25 torr, greater than 0 torr to 15 torr, greater than 0 torr to 10 torr, greater than 0 torr to 7.5 torr, greater than 0 torr to 5 torr, greater than 0 torr to 2.5 torr, greater than 0 torr to 2 torr, greater than 0 torr to 1 torr, greater than 0 torr to 0.75 torr, greater than 0 torr to 0.5 torr, greater than 0 torr to 0.25 torr, greater than 0 torr to 0.2 torr, greater than 0 torr to 0.1 torr, greater than 0 torr to 0.075 torr, greater than 0 torr to 0.05 torr, greater than 0 torr to 0.025 torr, greater than 0 torr to 0.02 torr, greater than 0 torr to 0.01 torr, or any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints.Exemplary ranges that take into account the partial pressure of one or more oxygen-containing gases having a relatively high lower limit include from 0.001 torr to 50 torr, from 0.001 torr to 30 torr, from 0.001 torr to 25 torr, from 0.001 torr to 10 torr, from 0.001 torr to 5 torr, from 0.001 torr to 1 torr, from 0.01 torr to 50 torr, from 0.01 torr to 25 torr, from 0.01 torr to 10 torr, from 0.01 torr to 5 torr, from 0.01 torr to 1 torr, or any range having any two of these values as endpoints, or any value within a range having any two of these values as endpoints.

[0077] One or more oxygen-containing gases present in the environment include one or more of water vapor, O2 gas, CO2 gas, NO2 gas, CO gas, hydrocarbon gases (including methane), and alcohol gases (including methanol, ethanol, and isopropyl alcohol). In addition, it is contemplated that one or more oxygen-containing gases are present at any one of the above ranges and values for at least 50% of the sublimation / distillation time, such as for at least 55% of the sublimation / distillation time, for at least 60% of the sublimation / distillation time, for at least 65% of the sublimation / distillation time, for at least 70% of the sublimation / distillation time, for at least 75% of the sublimation / distillation time, for at least 80% of the sublimation / distillation time, for at least 85% of the sublimation / distillation time, for at least 90% of the sublimation / distillation time, for at least 95% of the sublimation / distillation time, for at least 96% of the sublimation / distillation time, for at least 97% of the sublimation / distillation time, for at least 98% of the sublimation / distillation time, for at least 99% of the sublimation / distillation time, or for the entire sublimation / distillation time.

[0078] As described above, by minimizing the level of oxygen-containing gas in the environment, oxidation during the sublimation / distillation time can be minimized, thereby allowing an increase in the total pressure in the environment compared to previous rare earth element sublimation / distillation techniques. Since more heating gas can contact the solid composition, the higher total pressure can allow for faster and more complete sublimation / distillation by enhancing heat transfer to the sublimation / distillation material. For example, by restricting the level of oxygen-containing gas in the environment, such as restricting it to 10 torr or lower, 1 torr or lower, or any of the values and ranges considered above, the total pressure in the environment can be increased to 1 torr or higher, 2 torr or higher, 5 torr or higher, or 10 torr or higher, 25 torr or higher, 50 torr or higher, 100 torr or higher, 250 torr or higher, 500 torr or higher, 760 torr or higher, 1000 torr or higher, and 1520 torr or higher, while still minimizing oxidation, or any range with any two of these values as endpoints, or any value within a range with any two of these values as endpoints. Additionally, the higher total pressure can allow for a simpler and more cost-effective design that can be accomplished without the need for a pressure / vacuum vessel and expensive high-vacuum equipment. The higher total pressure can allow for more efficient transport of Yb in the gas phase to a surface (e.g., a collection surface) that is out of sight of the heating surface, thereby allowing for a more complex flow path, which helps to increase lutetium production and improve the separation ratio between ytterbium and lutetium. These increased total pressures can be achieved by introducing a non-reactive gas such as argon, krypton, xenon, or neon into chamber 105 and / or by introducing a gas that is reactive but does not react with ytterbium or lutetium and does not contain oxygen, such as hydrogen.

[0079] Still referring to Figure 1 and Figure 2, the temperature of sublimation and / or distillation (e.g., the temperature in the environment) can be in the range of 400°C to 2000°C, such as 450°C to 1500°C, 450°C to 1200°C, 450°C to 1000°C, 400°C to 1000°C, 400°C to 900°C, 400°C to 800°C, 450°C to 700°C, 400°C to less than 700°C, 400°C to 695°C, 450°C to 690°C, 450°C to 685°C, 450°C to 680°C, 450°C to 675°C, 450°C to 670°C, 450°C to 665°C, 450°C to 660°C, 450°C to 655°C, 450°C to 650°C, 450°C to 645°C, 450°C to 640°C, 450°C to 635°C, 450°C to 630°C, 450°C to 625°C, 470°C to about 630°C, 800°C to 2000°C, greater than 800°C to 2000°C, 1000°C to 2000°C, 1200°C to 2000°C, 1500°C to 2000°C, or any range with any two of these values as endpoints. In fact, the temperature of sublimation and / or distillation (e.g., the temperature in the environment) can be 400°C, 425°C, 450°C, 470°C, 475°C, 500°C, 525°C, 550°C, 575°C, 600°C, 625°C, 640°C, 650°C, 655°C, 660°C, 665°C, 670°C, 675°C, 680°C, 685°C, 690°C, 695°C, 698°C, 700°C, 725°C, 750°C, 775°C, 800°C, 850°C, 900°C, 950°C, 1000°C, 1100°C, 1200°C, 1300°C, 1400°C, 1500°C, 1600°C, 1700°C, 1800°C, 1900°C, 2000°C, any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints. Additionally, according to various embodiments, at any one of the above temperatures and temperature ranges, the ambient pressure range can be from 2000 torr to 1x10 -8 torr, from 1520 torr to 1x10 -8 torr, from 1000 torr to 1x10 -8 torr, from 760 torr to 1x10 -8 torr, from 700 torr to 1x10 -8 torr, from 500 torr to 1x10 -8 torr, from 250 torr to 1x10 -7 torr, from 100 torr to 1x10 -6 torr, from 1 torr to 1x10 -6 torr, 1x10 -1torr to 1x10 -6 torr, 1x10 -3 or lower, 1x10 -5 torr or lower, 1x10 -6 torr or lower, 2000 torr to 1x10 -1 torr, 1520 torr to 1 torr, 1000 torr to 1 torr, 760 torr to 1 torr, 760 torr to 250 torr, any range with any two of these values as endpoints, or any value within the range with any two of these values as endpoints.

[0080] The time periods required for the sublimation and / or distillation steps (e.g., within the sublimation / distillation time) can vary widely and depend on the amount of material in the solid composition, temperature, and pressure. The time periods required for the sublimation and / or distillation steps can range from 1 second to 1 week. In some embodiments, the rate of sublimation or distillation is related to the time issue. In some embodiments, the rate of sublimation or distillation can be a rate of 10 min / g to 100 min / g of the solid composition, or a rate of 20 min / g to 60 min / g of the solid composition. In one embodiment, the rate can be 40 min / g of the solid composition.

[0081] Referring again to Figure 1 and Figure 2 , generally, the preliminary purification process by distillation and / or sublimation is carried out as follows. The enriched Yb-176 metal target is encapsulated in a tube that can be sealed at both ends. For example, the tube can be a quartz tube, and the tube can have a diameter in the range of 0.5 cm to 2 cm, such as a diameter of 1 cm. Then the tube is sealed in an outer package (such as aluminum), which is suitable for irradiation and impermeable to water or air. The sealed outer package is irradiated by a reactor or other neutron source for several hours to several days (depending on the flux and batch requirements) to generate Lu-177 in the Yb-176 target. Then the sealed outer package is loaded into a processing hot cell or isolator. Inside the hot cell or isolator, which can include an inert environment, the irradiated ytterbium metal target is removed and placed in crucible 190 and placed in the vacuum chamber of the sublimation / distillation device 100, where the partial pressure of one or more oxygen-containing gases is reduced. To reduce the partial pressure of one or more oxygen-containing gases, an inert gas such as He, N2, and Ar can be introduced into the environment to displace the oxygen-containing gases. Additionally, or as an alternative, the pressure in the environment can be reduced, thereby reducing the partial pressure of all gases in the environment, including the oxygen-containing gases.

[0082] Then, a heating element 170 is used to heat the crucible 190, for example, to a first temperature by radio frequency (RF) induction. At the first temperature, due to the design of a leakage channel for a small amount of Yb vapor, the direct sublimation of Yb is indicated by a slight increase in the pressure inside the vacuum chamber. When Yb metal sublimes from the heated crucible, it deposits onto a collection surface, which can be actively cooled for collection and reuse. The sublimation continues for 30 to 50 minutes per gram of starting material (e.g., approximately 40 minutes per gram of starting material), and the completion of the process is determined by a sudden drop in the vacuum pressure from about 5x10 -6 torr to less than about 1x10 -6 torr, or alternatively, by a drop in the H2 signal to the threshold level of H2 gas or below.

[0083] As the sublimation progresses or after the sublimation is completed, the crucible 190 can be heated to a second temperature, which is higher than the first temperature. At this stage of the process, the generated lutetium or lutetium oxide, trace amounts of ytterbium or ytterbium oxide, and trace contaminants remain in the crucible 190. After the crucible 190 is cooled to a threshold temperature, for example, cooled to a threshold temperature of 90 °C or lower, the contents of the crucible including lutetium are dissolved in an acid to remove the substances dissolved in the acid from the crucible and transfer them to a chromatographic separation device. The crucible 190 can be passively cooled (e.g., by removing the heat applied through the heating element 170 and waiting for a period of time for heat conduction) or actively cooled (e.g., using flowing gas or liquid).

[0084] As described herein, any of the above lutetium compositions or lutetium-enriched samples can be subjected to chromatographic separation to further enrich lutetium in the composition or sample. Such chromatographic separation can include column chromatography, plate chromatography, thin-layer chromatography, or high-performance liquid chromatography. Illustrative processes for the purification of lutetium can be as described in U.S 7,244,403 and 9,816,156, both of which are hereby incorporated by reference in their entireties for reference. However, it should be understood that other chromatographic separation techniques can be used to further enrich lutetium separated using the techniques described herein. In one aspect, the process can include dissolving the lutetium and ytterbium composition retained in the crucible during sublimation in an acid and applying the resulting solution to a chromatographic column or chromatographic plate. This may include plate chromatographic materials, chromatographic columns, high-performance liquid (HPLC) chromatographic columns, ion exchange columns, etc.

[0085] As an illustrative example, a solution of lutetium in dilute HCl (i.e., HCl of 0.01 N to 5 N) can be prepared. This solution can be applied to a solution-filled or dried ion exchange column, and lutetium is eluted with an additional rinse of dilute HCl. This is generally described in U.S. 7,244,403 as the solution being usually a dilute solution of a strong acid (usually HCl) that is easy to handle. The resin bed can be in the form of a strong anion exchange resin in the column, and contact occurs by passing the solution through the column. In some embodiments, the resin is a strongly basic anion exchange resin with a cross-linking degree of about 8%. First, the HCl solution is passed through the column to form an HCl-treated column, then the NaCl solution is passed through the HCl-treated column to form an NaCl-treated column, and then sterile water is passed through the NaCl-treated column. These preparation steps help to elute a sterile and pyrogen-free product. The resin can then be dried before applying the lutetium solution. In some embodiments, the anion exchange resin is in powder form, typically having particles sized from 100 mesh to 200 mesh. To accelerate the flow rate of the solution through the column, a sterile gas pressure can be applied to the head of the column. This can be achieved by injecting sterile gas, preferably air, into the upper end of the column to push the Lu-177 solution through the column. The purity of the Lu-177 recovered by this process can be higher than the purity before column chromatography through the anion exchange column.

[0086] In another aspect, the process can include purifying lutetium from a composition that also includes ytterbium using a cation exchange resin. As an illustrative example, and as generally described in U.S. 9,816,156, the method includes: loading a first column filled with a cation exchange material, wherein a Lu / Yb mixture is dissolved in an inorganic acid, exchanging the protons of the cation exchange material with ammonium ions using an NH4Cl solution, and washing the cation exchange material of the first column with water. The outlet of the first column is connected to the inlet of a second column, which is also filled with a cation exchange material. Then, water and a chelating agent are applied to the columns in a gradient starting from 100% H2O to 0.2 M of the chelating agent at the inlet of the first column in order to elute lutetium from the first and second columns. Illustrative examples of chelating agents include, but are not limited to, α-hydroxyisobutyrate [HIBA], citric acid, citrate, butyric acid, butyrate, EDTA, EGTA, and ammonium ions. The method can also include: measuring the radioactivity dose at the outlet of the second column to identify the elution of the Lu-177 compound; and collecting the first Lu-177 eluate from the outlet of the second column into a container, followed by protonating the chelating agent to inactivate the chelating agent so that it cannot form a complex with Lu-177. The method can also include: loading a final column filled with a cation exchange material by continuously delivering an acidic lutetium eluate to the inlet of the final column, rinsing off the chelating agent with a dilute inorganic acid having a concentration lower than about 0.1 M, removing trace amounts of other metal ions from the lutetium solution by rinsing the cation exchange material of the final column with different concentrations of inorganic acid in the range of about 0.01 M to 2.5 M; and eluting Lu-177 ions from the final column with a high concentration of inorganic acid in the range of about 1 M to 12 M. Finally, an eluate containing lutetium of higher purity than that applied to the columns can be collected, and the solvent and inorganic acid can be removed by evaporation.

[0087] In another aspect, the process can include: dissolving a lutetium and ytterbium composition or a ytterbium-rich sample in an acid to form a dissolved Lu / Yb solution, adding a chelating agent to the dissolved Lu / Yb solution and neutralizing with a base to form a chelated Lu / Yb solution containing chelated lutetium and ytterbium, and subjecting the chelated solution to chromatography, collecting the purified chelated lutetium fraction, and dechelating the lutetium to obtain purified lutetium. The lutetium purity of the purified chelated lutetium fraction is higher than the lutetium purity in the dissolved Lu / Yb solution. High purity levels of lutetium can be obtained using such a chromatographic process. For example, the purified lutetium obtained after chromatography and post-treatment can include Lu-177 having an isotopic purity greater than 99%. This includes Lu-177 having an isotopic purity greater than 99.9%, greater than 99.99%, greater than 99.999%, or greater than 99.9999%.

[0088] Generally, ytterbium metal or metal oxide targets are irradiated to form Lu-177. The target is then dissolved in acid, a chelating agent is added, and the solution is neutralized with base to form a chelated metal. Chromatographic separation is carried out, and then the purified metal is decomplexed / dedechelated from the chelating agent. However, due to the limitations of chromatography, starting from an impure lutetium source (i.e., irradiated ytterbium oxide target), the efficiency of chromatography is low, and even on a preparative scale, only small fractions of purified lutetium can be obtained per chromatographic cycle. As described above, using purified lutetium after distillation / sublimation provides unexpected benefits in producing higher purity rare earth metals, especially lutetium, on a larger scale and in a shorter time, which cannot be achieved by distillation or chromatography alone.

[0089] The initial dissolution of lutetium in acid can be carried out using hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, persulfuric acid, perchloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, or a mixture of any two or more thereof. The concentration of the acid can be from 0.01 M to 6 M and / or the concentration of the base can be from 0.01 M to 6 M. This includes concentrations from 1 M to 6 M and from 2 M to 6 M. Then only the chelating agent is added together with a base (such as lithium hydroxide, sodium hydroxide, potassium hydroxide, NH4OH, or alkyl ammonium hydroxide) to neutralize the acid and produce chelated lutetium. At this time, the chelated 177 Lu does contain other impurities. For example, it will contain Yb and may also contain K, Na, Ca, Fe, Al, Si, Ni, Cu, Pb, La, Ce, Lu (except Lu-177), Eu, Sn, Er, and Tm. Then HPLC is carried out. HPLC can be carried out on a suitable chromatographic column and eluted with a suitable mobile phase, and each can vary under different method development scenarios. As an example, the chromatographic column can be a cation exchange column, an anion exchange column, a reversed-phase C18 column, etc., and the mobile phase can be any mobile phase determined to achieve separation.

[0090] For further purification, the chelated 177 Lu is applied to a high-performance liquid chromatography (HPLC) system (a reversed-phase C18 column with 12 vol% to 14 vol% methanol), and then the chelated 177 Lu is eluted from the system with a higher purity than when applied to the chromatographic column. The chelated 177 Lu is acidified with HCl and released from the chelating agent as a chloride salt.

[0091] The mobile phase can be water-based or organic solvent-based. Illustrative examples include but are not limited to water, alcohols, alkanes, ethers, esters, acids, bases, and aromatic compounds. In different embodiments, the mobile phase can include water, methanol / water, methanol / trifluoroacetic acid / water, and / or methanol mobile phases.

[0092] After purifying lutetium chelate by HPLC, a dechelation process is carried out to obtain purified lutetium as a lutetium solution and / or ionic material. In some embodiments, the dechelation includes contacting the purified lutetium chelate fraction with an acid, which is hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, persulfuric acid, perchloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, or a mixture of two or more thereof. The concentration of the acid can be from 0.01 M to 6 M and / or the concentration of the base is from 0.01 M to 6 M. This includes concentrations from 1 M to 6 M and from 2 M to 6 M.

[0093] As described above, the processes described herein can be used for the separation of lutetium and ytterbium. However, it can be used to separate any of the rare earths and / or actinides in which there are differences in boiling point / sublimation point, and then further purified using chromatographic separation in the presence of various chelating agents. Among the above chelating agents, the rare earth elements that can be chelated for purification include cerium (Ce), dysprosium (Dy), erbium (Er), europium (Eu), gadolinium (Gd), holmium (Ho), lanthanum (La), lutetium (Lu), neodymium (Nd), praseodymium (Pr), promethium (Pm), samarium (Sm), scandium (Sc), terbium (Tb), thulium (Tm), ytterbium (Yb), and yttrium (Y). In some embodiments, the method includes chromatographically separating a rare earth element from a mixture of at least two metal ions, wherein at least one of the metal ions is Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Pm, Sm, Sc, Tb, Tm, Yb, or Y.

[0094] As used herein, the terms "approximate", "about", "substantially", and similar terms are intended to have a broad meaning, consistent with the common and accepted usage of those of ordinary skill in the art to which the subject matter of this disclosure pertains. Those skilled in the art who read this disclosure should understand that these terms are intended to allow the description of certain features being described and claimed without restricting the scope of these features to the exact numerical values or ideal geometric forms provided. Thus, these terms should be interpreted to indicate that non-substantive or immaterial modifications or alterations to the subject matter being described and claimed are considered to be within the scope of the disclosure as set forth in the appended claims.

[0095] As used herein, the term "connected" and its variants refer to two elements being connected to each other either directly or indirectly. Such connection can be stationary (e.g., permanent or fixed) or movable (e.g., detachable or releasable). Such connection can be achieved by directly connecting the two elements together, or by using separate intermediate elements and any additional intermediate elements to connect the two elements to each other, or by using an intermediate element that is integrally formed as a single unit with one of the two elements to connect the two elements to each other. If "connected" or its variants are modified by additional terms (e.g., directly connected), the general definition of "connected" above will be modified by the ordinary language meaning of the additional term (e.g., "directly connected" means the connection of two elements without any separate intermediate element), resulting in a narrower definition than the general definition of "connected" above. Such connection can be mechanical, electrical, optical, or fluidic.

[0096] References herein to the position of elements (e.g., "top", "bottom", "above", "below") are for purposes of describing the orientation of the various elements in the figures only. It should be noted that the orientation of the various elements can vary according to other exemplary embodiments, and such variations are intended to be included in the present disclosure.

[0097] Although the figures and description may show a particular order of method steps, the order of these steps can be different from that shown and described, unless otherwise specified above. Additionally, two or more steps can be performed simultaneously or partially simultaneously, unless otherwise specified above. Such variations can depend, for example, on the software and hardware systems selected and the choices of the designer. All such variations are within the scope of the present disclosure. Similarly, the software implementation of the method can be achieved by standard programming techniques, where rule-based logic and other logics are employed to implement the various connection steps, processing steps, comparison steps, and decision steps.

[0098] Although specific embodiments have been illustrated and described herein, it should be understood that various other changes and modifications can be made without departing from the spirit and scope of the claimed subject matter. Additionally, although various aspects of the claimed subject matter have been described herein, these aspects need not be used in combination. Accordingly, the appended claims are intended to cover all such changes and modifications within the scope of protection of the claimed subject matter.

Claims

1. A method for purifying lutetium, the method comprising: In an environment with a temperature range of 400 °C to 2000 °C, ytterbium is sublimated or distilled from a solid composition containing ytterbium and lutetium over a sublimation / distillation time to leave a lutetium composition, the lutetium composition containing a higher weight percentage of lutetium than present in the solid composition, wherein the environment contains water vapor and the water vapor is present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation time.

2. The method according to claim 1, wherein, The water vapor is present in the environment at a partial pressure of 1.5 torr or less for at least 95% of the sublimation / distillation time.

3. The method according to claim 1, wherein, The water vapor is present in the environment at a partial pressure of 0.1 torr or less during the sublimation / distillation time.

4. The method according to claim 1, wherein, The solid composition ranges from 0.5 g to 10 g at the start of the sublimation / distillation time.

5. The method according to claim 1, wherein, The water vapor is present in the environment at a partial pressure of 0.001 torr to 1.5 torr during the sublimation / distillation time.

6. The method according to claim 1, wherein, The environment includes one or more of the following: O2 gas, wherein the O2 gas is present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation time; CO2 gas, wherein the CO2 gas is present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation time; NO2 gas, wherein the NO2 gas is present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation time; and CO gas, wherein the CO gas is present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation time.

7. The method according to claim 1, wherein, The solid composition is contained in a crucible of a sublimation / distillation system, and sublimating or distilling from the solid composition includes heating the crucible such that ytterbium sublimates, distills, or both sublimates and distills from the solid composition and is collected on a collection surface of the sublimation / distillation system, wherein the sublimation / distillation system further includes a residual gas analyzer configured to detect one or more gases present in the environment.

8. The method according to claim 7, wherein, The method further includes: Detecting H2 gas with the residual gas analyzer while sublimating or distilling ytterbium from the solid composition; and After detecting that the H2 gas is at or below a threshold level, reducing the temperature in the environment to 90 °C or lower.

9. The method according to claim 8, wherein, The threshold level includes 0.1 ppm of H2.

10. A method for purifying lutetium, the method comprising: In an environment with a temperature range of 400 °C to 2000 °C, ytterbium is sublimated or distilled from a solid composition containing ytterbium and lutetium over a sublimation / distillation time to leave a lutetium composition, the lutetium composition containing a higher weight percentage of lutetium than present in the solid composition, wherein the environment contains one or more oxygen-containing gases and the one or more oxygen-containing gases are present in the environment at a total partial pressure of 10 torr or less during the sublimation / distillation time.

11. The method according to claim 10, wherein, The one or more oxygen-containing gases contain a total partial pressure of 10 torr or less in the environment for at least 95% of the sublimation / distillation time.

12. The method according to claim 10, wherein, The one or more oxygen-containing gases are present in the environment at a total pressure of 1 torr or less during the sublimation / distillation time.

13. The method according to claim 10, wherein, The total pressure in the environment is 10 torr or greater during the sublimation / distillation time.

14. The method according to claim 10, wherein, The one or more oxygen-containing gases are present in the environment at a total pressure in the range of 0.01 torr to 10 torr during the sublimation / distillation time.

15. The method according to claim 10, wherein, The one or more oxygen-containing gases present in the environment include one or more of water vapor, O2 gas, CO2 gas, NO2 gas, CO gas, hydrocarbon gas, and alcohol gas.

16. The method according to claim 10, wherein, The solid composition is contained in a crucible of a sublimation / distillation system, and sublimating or distilling from the solid composition includes heating the crucible such that ytterbium sublimates, distills, or both sublimates and distills from the solid composition and is collected on a collection surface of the sublimation / distillation system; and wherein the sublimation / distillation system further includes a residual gas analyzer configured to detect one or more gases present in the environment.

17. The method according to claim 16, wherein, The method further includes: detecting H2 gas with the residual gas analyzer while sublimating or distilling ytterbium from the solid composition; and after detecting that the H2 gas is at or below a threshold level, reducing the temperature in the environment to 90 °C or lower.

18. A method for purifying lutetium, the method comprising: In an environment having a temperature range of 400 °C to 2000 °C, ytterbium is sublimated or distilled from a solid composition containing ytterbium and lutetium over a sublimation / distillation time to leave a lutetium composition that contains a higher weight percentage of lutetium than is present in the solid composition; wherein the environment contains one or more oxygen-containing gases, and the one or more oxygen-containing gases are present in the environment at a total pressure of 1.5 torr or less during the sublimation / distillation time; wherein one of the one or more oxygen-containing gases includes water vapor, and the water vapor is present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation time; and wherein the total pressure in the environment is 2 torr or greater during the sublimation / distillation time.

19. The method according to claim 18, wherein The method further includes: detecting H2 gas in the environment with a residual gas analyzer while sublimating or distilling ytterbium from the solid composition; and after detecting that the H2 gas is at or below a threshold level, reducing the temperature of the environment to 90 °C or lower.

20. The method according to claim 18, wherein The one or more oxygen-containing gases are present in the environment at a total pressure in the range of 0.01 torr to 10 torr during the sublimation / distillation time.

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