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

Abstract

A method of purifying lutetium includes sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature in the range of 400°C to 2000°C over a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in the solid composition, the environment comprising water vapor, and the water vapor being present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation period.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 404,080, filed September 6, 2022, which is incorporated herein by reference in its entirety.

[0002] This disclosure relates generally to the separation of rare earth elements and their purification. More particularly, this disclosure relates to the isolation and purification of lutetium from irradiated targets containing other rare earth metals, such as ytterbium. [Background technology]

[0003] Lutetium-177 (Lu-177) is a radioisotope 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 Lu-177 during their treatment.

[0004] Therefore, there is a need for improved techniques for separating and purifying radioisotopes such as Lu-177. Summary of the Invention

[0005] According to a first aspect of the present disclosure, a method of purifying lutetium includes sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature in the range of 400°C to 2000°C over a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in the solid composition, the environment comprising water vapor, the water vapor being present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation period.

[0006] A second embodiment includes the method of the first embodiment, wherein the water vapor is at a partial pressure of 1.5 torr or less in the environment for at least 50% of the sublimation / distillation period.

[0007] A third embodiment includes the method of the first embodiment or the second embodiment, wherein the water vapor is at a partial pressure of 1.5 torr or less in the environment for at least 75% of the sublimation / distillation period.

[0008] A fourth embodiment includes the method of any of the preceding embodiments, wherein the water vapor is at a partial pressure of 1.5 torr or less in the environment for at least 95% of the sublimation / distillation period.

[0009] A fifth embodiment includes the method of any of the preceding embodiments, wherein water vapor is at a partial pressure of 1.5 torr or less in the environment throughout the sublimation / distillation period.

[0010] A sixth aspect includes the method of any of the preceding aspects, wherein water vapor is present in the environment at a partial pressure of 1 torr or less.

[0011] A seventh aspect includes the method of any of the preceding aspects, wherein water vapor is present in the environment at a partial pressure of 0.1 torr or less.

[0012] An eighth embodiment includes the method of any of the preceding embodiments, wherein the environment includes O2 gas, and the O2 gas is present in the environment at a partial pressure of 1 torr or less.

[0013] A ninth aspect includes the method of the eighth aspect, wherein O2 gas is present in the environment at a partial pressure of 0.1 torr or less.

[0014] A tenth aspect includes the method of the eighth or ninth aspect, wherein O2 gas is present in the environment at a partial pressure of 0.01 torr or less.

[0015] An eleventh aspect includes the method of any of the preceding aspects, wherein the environment comprises CO2 gas, and the CO2 gas is present in the environment at a partial pressure of 1 torr or less.

[0016] A twelfth aspect includes the method of the eleventh aspect, wherein CO2 gas is present in the environment at a partial pressure of 0.1 torr or less.

[0017] A thirteenth aspect includes the method of the eleventh or twelfth aspects, wherein CO2 gas is present in the environment at a partial pressure of 0.01 torr or less.

[0018] A fourteenth aspect includes the method of any of the preceding aspects, wherein the environment includes NO2 gas, and the NO2 gas is present in the environment at a partial pressure of 1 torr or less.

[0019] A 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 less.

[0020] A 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 less.

[0021] A seventeenth aspect includes the method of any of the preceding aspects, wherein the environment comprises CO gas, and the CO gas is present in the environment at a partial pressure of 1 torr or less.

[0022] An eighteenth embodiment includes the method of the seventeenth embodiment, wherein the CO gas is present in the environment at a partial pressure of 0.1 torr or less.

[0023] A nineteenth aspect includes the method of the seventeenth aspect or the eighteenth aspect, wherein the CO gas is present in the environment at a partial pressure of 0.01 torr or less.

[0024] A twentieth aspect includes the method of any of the preceding aspects, wherein the solid composition is contained in a crucible of a sublimation / distillation system, and wherein sublimating or distilling the ytterbium from the solid composition comprises heating the crucible such that the ytterbium sublimes, distills, or sublimes and distills from the solid composition and collects on a collection surface of the sublimation / distillation system.

[0025] A twenty-first aspect includes the method of the twentieth aspect, wherein the sublimation / distillation system further comprises a residual gas analyzer configured to detect one or more gases present in the environment.

[0026] A twenty-second aspect includes the method of the twenty-first aspect, further including the steps of detecting H gas with a residual gas analyzer while sublimating or distilling the ytterbium from the solid composition, and reducing the temperature in the environment to 90° C. or less after detecting H gas at a level below a threshold level.

[0027] A twenty-third aspect includes the method of the twenty-second aspect, wherein the threshold level comprises 0.1 ppm H2.

[0028] A twenty-fourth aspect includes the method of any of the preceding aspects, further including collecting the ytterbium for reuse.

[0029] A 25th aspect includes the method of any of the preceding aspects, wherein the environment is 1×10 -8 A reduced pressure environment is provided with a reduced pressure in the range of 0.1 torr to 700 torr.

[0030] A twenty-sixth embodiment includes the method of the twenty-fifth embodiment, wherein the reduced pressure is 1×10 -3 torr or less.

[0031] A 27th aspect includes the method of any of the previous aspects, wherein the temperature is in the range of 450°C to 1500°C.

[0032] A 28th embodiment includes the method of any of the preceding embodiments, wherein the temperature is less than 700°C.

[0033] A twenty-ninth aspect includes the method of any of the preceding aspects, further including the step of chromatographically separating the lutetium composition to further enrich the lutetium in the lutetium composition.

[0034] A 30th aspect includes the method of the 29th aspect, further including the steps of dissolving a 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 chelated lutetium and chelated ytterbium; chromatographically separating the chelated lutetium solution to collect a purified chelated lutetium fraction; and dechelating the lutetium to obtain purified lutetium.

[0035] A thirty-first embodiment includes the method of the thirtieth embodiment, wherein the purified chelated lutetium fraction has a purity of lutetium that is greater than the purity of lutetium in the dissolved lutetium solution.

[0036] A thirty-second aspect includes the method of the thirty-first aspect, wherein the dechelating step comprises contacting the purified chelated lutetium fraction with an acid that is hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, peroxosulfuric acid, perchloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, or a mixture of any two or more thereof.

[0037] According to a thirty-third aspect of the present disclosure, a method of purifying lutetium includes sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature in the range of 400°C to 2000°C over a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in the solid composition, the environment comprising one or more oxygen-containing gases, the one or more oxygen-containing gases being present in the environment at a total partial pressure of 10 torr or less during the sublimation / distillation period.

[0038] A thirty-fourth embodiment includes the method of the thirty-third embodiment, wherein the one or more oxygen-containing gases comprise a total partial pressure of 10 torr or less in the environment for at least 50% of the sublimation / distillation period.

[0039] A thirty-fifth embodiment includes the method of the thirty-third or thirty-fourth embodiment, wherein the one or more oxygen-containing gases comprise a total partial pressure of 10 torr or less in the environment for at least 75% of the sublimation / distillation period.

[0040] A thirty-sixth embodiment includes the method of any of the thirty-third to thirty-fifth embodiments, wherein the one or more oxygen-containing gases comprise a total partial pressure of 10 torr or less in the environment for at least 95% of the sublimation / distillation period.

[0041] A thirty-seventh embodiment includes the method of any of the thirty-third through thirty-sixth embodiments, wherein the one or more oxygen-containing gases comprise a total partial pressure of 10 torr or less in the environment throughout the sublimation / distillation period.

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

[0043] A thirty-ninth embodiment includes the method of any of the thirty-third through thirty-eighth embodiments, wherein the total partial pressure of the one or more oxygen-containing gases present in the environment is 0.001 torr or less.

[0044] A fortieth aspect includes the method of any of the thirty-third to thirty-ninth aspects, wherein the one or more oxygen-containing gases present in the environment include one or more of water vapor, O gas, CO gas, NO gas, CO gas, hydrocarbon gas, and alcohol gas.

[0045] A forty-first embodiment includes the method of any of the thirty-third to fortieth embodiments, wherein the total pressure in the environment is greater than or equal to 10 torr during the sublimation / distillation period.

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

[0047] According to a forty-third aspect of the present disclosure, a method of purifying lutetium includes sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature in the range of 400°C to 2000°C over a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in the solid composition, wherein the environment comprises one or more oxygen-containing gases, wherein the 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 period, one of the one or more oxygen-containing gases comprises water vapor, wherein the water vapor is present in the environment at a partial pressure of 0.1 torr or less during the sublimation / distillation period, and the total pressure in the environment is 1 torr or greater during the sublimation / distillation period.

[0048] A 44th aspect includes the method of the 43rd aspect, further including the steps of detecting H gas in the environment with a residual gas analyzer while sublimating or distilling the ytterbium from the solid composition, and reducing the temperature in the environment to 90° C. or less after detecting H gas at a level below a threshold level.

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

[0050] A 46th embodiment includes the method of any of the preceding embodiments, wherein the solid composition is in the range of 0.5 g to 10 g at the start of the sublimation / distillation period.

[0051] A 47th aspect includes the method of any of the preceding aspects, wherein water vapor is present in the environment during the sublimation / distillation period at a partial pressure of between 0.001 torr and 1.5 torr.

[0052] These and further features provided by the embodiments described herein will be more fully understood when considered in conjunction with the drawings and the following detailed description.

[0053] The embodiments set forth in the drawings are illustrative and exemplary in nature and are not intended to limit the scope of the invention as 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 structure is indicated with like numerals and in which: [Brief explanation of the drawings]

[0054] [Figure 1] 1 is a Txy diagram for lutetium and ytterbium at a constant pressure of 1 μTorr. [Figure 2] FIG. 1 is a schematic diagram of a chamber for distillation / sublimation of ytterbium and lutetium according to one or more embodiments shown and described herein. DETAILED DESCRIPTION OF THE INVENTION

[0055] Referring generally to the drawings, embodiments of the present disclosure are directed to methods for separating rare earth elements using sublimation or distillation processes in a high-temperature environment with low partial pressures of specific gases, such as oxygen-containing gases, that react with the rare earth elements. For example, embodiments of the present disclosure are directed to separating lutetium from a composition (e.g., a solid composition) containing ytterbium and lutetium to obtain high-purity lutetium, e.g., a high-purity isotope of lutetium, such as Lu-177. Upon decay, Lu-177 emits low-energy beta particles suitable for treating tumors, making it useful in numerous medical applications. It also emits two gamma rays that can be used for diagnostic testing. Isotopes with both therapeutic and diagnostic properties are referred to as "theranostics." In addition to being a theranostic, Lu-177 also has a half-life of 6.65 days, which allows for more complex chemistries and facilitates easy global distribution. Lu-177 also exhibits chemical properties that allow it to be conjugated to a large number of biomolecules for a wide range of therapeutic applications.

[0056] There are two main routes to producing Lu-177. One is via neutron capture reaction with 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 gas) or a similar isotope of an element in the same chemical form as the target isotope. In microchemistry, the target chemical element or isotope does not behave chemically as expected due to its extremely low concentration. Furthermore, isotopes of the same element are not chemically separable and require mass separation techniques. Therefore, Lu-177 produced via the carrier method has limited medical applications.

[0057] The second method of producing Lu-177 is the neutron capture reaction of ytterbium-176 (Yb-176) with Yb-176 (Yb-176(n,γ)Yb-177) to produce Yb-177, which rapidly decays (t = 1.911 hours). 1 / 2 It undergoes beta decay (at 400 kJ / s) to Lu-177. Impurities of Yb-174 are commonly present in Yb-176, resulting in an additional impurity of Lu-175 in the final product. This process is considered a "carrier-free" process. The process can be carried out as ytterbium metal or ytterbium oxide.

[0058] This disclosure describes a process for the separation of Yb and Lu obtained from a carrier-free process. The process includes a distillation / sublimation process to purify lutetium and remove excess Yb after irradiation. The process may also include further purification of the lutetium using a chromatographic separation process. Because the amount of material that can be processed in any one run during chromatographic separation is limited, a process for concentrating Lu prior to chromatographic separation allows for scaling of the recovery of product Lu to higher levels than previously obtainable. For example, current processes for chromatographic separation by itself are limited to a 20-milligram target per pass, requiring processing times of 30 minutes to 1 hour for each pass. Combining distillation / sublimation and chromatographic separation allows for the use of larger targets and the isolation of products by distillation that can then be passed on to the chromatographic process. Processing a 20-gram sample by chromatography alone would require 1,000 batches, resulting in significant material loss.

[0059] Separation of Yb and Lu may utilize, at least in part, the difference in their vapor pressures at a particular temperature and pressure. As an example, at standard temperature and pressure, the boiling point of Yb is 1196°C, and the boiling point of Lu is 3402°C. The difference in vapor pressures at a particular temperature and pressure can be used to separate Yb and Lu by sublimation and / or distillation. Referring now to FIG. 1, graph 50 is a Txy diagram for lutetium and ytterbium at a constant pressure of 1 μTorr. In FIG. 1, line 54 shows the condensed phase composition at a given temperature (i.e., bubble point), and line 52 shows the vapor phase (i.e., dew point). Graph 50 was generated using ideal gas and solution assumptions valid at low pressure and high temperature, as well as the chemical similarity of the two components.

[0060] In sublimation, the solid phase of an element is converted directly to a gas phase by heating, which can then be collected for later use. In distillation, the solid is heated (via the liquid phase) to its boiling point and evaporated, and the evaporated fraction can be recovered downstream after the vapor is condensed. In this case, ytterbium is evaporated, leaving a material enriched in lutetium (which can be collected downstream for later use). This can be done on a larger scale, thus increasing the amount of available lutetium. Furthermore, the collected Yb is available for recycling to a reactor that produces more Lu in a later process run.

[0061] Referring now to FIG. 2, a schematic diagram of a sublimation / distillation apparatus 100 for separating rare earth elements, such as lutetium and ytterbium, is shown. The sublimation / distillation apparatus 100 includes a chamber 105 with gas, cooling, vacuum, power, and instrumentation feedthroughs. The sublimation / distillation apparatus 100 can generate environments within the chamber 105 with various conditions, such as high temperature, low pressure, high levels of inert gas, and low partial pressure of selected gases. The sublimation / distillation apparatus 100 includes a crucible 190 and a heating element 170, both of which may be housed within the chamber 105. The chamber 105 may also include a sealable access port 110 that provides a user with selective access to the crucible 190, for example, to access and transfer a sample contained therein. The crucible 190 may be made of a refractory material (e.g., molybdenum or tantalum). In some embodiments, heating element 170 is an induction heating element, such as an RF induction coil. Crucible 190 can be suspended or supported within the RF induction heating coil. Temperature sensor 180 monitors the temperature of crucible 190, and pressure sensing instrument 140 monitors the overall pressure of chamber 105 and the partial pressure of one or more gases of interest, such as an oxygen-containing gas. In some embodiments, pressure sensing instrument 140 includes one or more gases present in the environment, such as a residual gas analyzer configured to detect the partial pressure of one or more gases present in the environment. Sublimation / distillation apparatus 100 also includes a vacuum pump connection 150 and at least one port 200 for the introduction of an inert gas.

[0062] The sublimation / distillation apparatus 100 includes a collection surface 160 that forms a cold surface. The collection surface 160 may be actively cooled by a cooling water line 130. The temperature of the collection surface 160 may be monitored by a temperature sensor 120. In some embodiments, the collection surface 160 may include a cold finger 165 (e.g., a cooling rod) extending from the collection surface 160 toward the crucible 190 and positioned directly above the crucible 190. The cold finger 165 and the collection surface 160 are movable, such that an open end of the crucible 190 can be open to a vacuum system (e.g., open to the chamber 105) or can be sealed to the collection surface 160. In some embodiments, the cold finger 165 includes an end effector. In practice, the cold finger 165 may extend from the collecting surface 160 toward the crucible 190 such that the cold finger 165 extends into the crucible 190 when the collecting surface 160 is sealed onto the crucible 190. Like the collecting surface 160, the cold finger 165 may also be actively cooled. In other embodiments, the collecting surface 160 may be a surface (e.g., an inner surface) of the collecting crucible. The collecting crucible may be a second crucible having an open end oriented facing the open end of the crucible 190.

[0063] 2, a method for separating and purifying lutetium from a composition comprising lutetium and ytterbium (e.g., solid composition 102) is described herein. The method includes sublimating or distilling ytterbium from solid composition 102 at a temperature of 400° C. to 2000° C. over a sublimation / distillation period in an environment having a low partial pressure of one or more oxygen-containing gases, such as HO gas (i.e., water vapor), O gas, CO gas, CO gas, NO gas, hydrocarbon gases (including methane), and alcohol gases (including methanol, ethanol, and isopropyl alcohol), to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in solid composition 102. In practice, at the start of the separation process, solid composition 102 is contained in crucible 190, and sublimating or distilling ytterbium from solid composition 102 comprises heating crucible 190, for example with heating element 170, such that ytterbium sublimes, distills, or sublimes and distills from solid composition 102 and accumulates on collection surface 160, in some embodiments on cold finger 165, and in some embodiments on the inner surface of the collection crucible. As noted above, ytterbium sublimated / distilled from the solid composition can be recycled as additional target material for irradiation and reuse later in the separation process.

[0064] The sublimation / distillation process results in a sample ("lutetium composition") that is enriched in lutetium relative to the solid composition entering the process. At the start of the sublimation / distillation process (e.g., at the start of the sublimation / distillation period), the solid composition can have a mass in the range of 0.1 grams (g) to 15 g, 0.5 g to 10 g, 1 to 10 g, 1 to 5 g, 1 to 2 g, etc., 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, etc., any range having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints. Yield and purity can be measured in a number of ways. For example, in some embodiments, the process results in a reduction in the ytterbium mass of the solid composition of 1000:1 to 10,000:1. In other words, after the sublimation / distillation is complete, there is 1,000 to 10,000 times less ytterbium in the sample than before the process (i.e., than was present in the solid composition). The recovered lutetium composition (i.e., the contents of the acid-dissolved crucible) may, in some embodiments, contain 1% to 90% by weight of ytterbium relative to the total remaining mass, which is subsequently separated in a chromatographic process, as described below. In other embodiments, the ytterbium collected from the sublimation / distillation is collected in an amount of 90% to 99.999% by weight of the ytterbium present in the solid composition. A purification step is also performed 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, and Tm may be removed. In other words, the method includes the step of performing sublimation, distillation, or a combination thereof on a sample containing Yb-176 and Lu-177 to remove at least a portion of the Yb-176 from the sample and the Lu-177 enriched sample.

[0065] It has been determined that purifications of greater than 1000:1 reduction in Yb (i.e., a 1000-fold reduction in the amount of Yb present) can be achieved, including greater than about 3000:1, greater than 8000:1, greater than 10000:1, and up to about 40000:1 inclusive. However, greater reductions in Yb may be necessary to meet purity requirements for some pharmaceutical products. Furthermore, additional purification may be performed prior to use in pharmaceutical applications. Such purification may be obtained through the use of chelating agents and / or chromatographic separation.

[0066] Furthermore, and without being bound by theory, reducing the relative amount of oxygen-containing gas in the environment during the sublimation / distillation period reduces oxidation reactions between the solid composition and the oxygen-containing gas. For example, ytterbium separated from the solid composition may react with water vapor to form Yb2O3 and H2 gas or Yb(OH)3 and H2 gas. By reducing oxidation, contaminants in the resulting separated lutetium and ytterbium may be minimized. Oxidation increases the concentration of ytterbium in the lutetium composition, thereby requiring more effort to purify the lutetium composition in a subsequent separation step, such as a chromatographic separation. Ytterbium is highly reactive and, at sublimation or distillation temperatures, readily reacts with and consumes oxygen species present in the environment, reducing otherwise stable molecules or substances. Because solid compositions typically contain less than 0.1% lutetium, increasing the oxidation of ytterbium may result in a higher concentration of the lutetium fraction in the lutetium composition. Furthermore, converting ytterbium to other non-metallic forms precludes its reuse as a metal target for irradiation, requiring further chemical conversion and further losses to return it to its metallic form.

[0067] On the other hand, it is difficult to completely purge the environment of oxygen-containing gas. In fact, in some embodiments, it is useful to have a small amount of water vapor or other oxygen-containing gas present in the environment. The pressure-sensing instrument 140 (e.g., a residual gas analyzer) of the sublimation / distillation apparatus 100 is configured to detect H gas. Without being bound by theory, H gas is an off-gas component of the sublimation process, where H O reacts with the Yb metal component of the solid composition to form Yb oxide or Yb hydroxide and H gas. The H gas is detected by the pressure-sensing instrument 140 (e.g., a residual gas analyzer) during the sublimation / distillation process and can be used to determine when the separation of lutetium and ytterbium from the solid composition is complete based on a decrease in the H detection signal. In some embodiments, the method includes detecting H gas with the pressure-sensing instrument 140 (e.g., a residual gas analyzer) while sublimating or distilling ytterbium from the solid composition. After detecting H gas at a level below a threshold level, the temperature in the environment is reduced to a threshold temperature. Thus, the presence of an oxygen-containing gas, albeit at a low level, facilitates greater control of the sublimation / distillation process. In some embodiments, the threshold temperature is 90°C or less, e.g., 85°C or less, 80°C or less, 75°C or less, 70°C or less, 65°C or less, 60°C or less, 55°C or less, 50°C or less, or any value in a range having any two of these values ​​as endpoints. Once the threshold temperature is reached, the separated lutetium and 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 of H2, e.g., 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 having any two of these values ​​as endpoints, or any value of H2 in a range having any two of these values ​​as endpoints.

[0068] In some embodiments, water vapor is present in the environment and has a partial pressure of 10 torr or less during the sublimation / distillation period, e.g., 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, 0.0 The partial pressure is present at a partial pressure of 0.05 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints. In other words, the water vapor is maintained at a partial pressure in the range of greater than 0 to 10 torr during the sublimation / distillation period, e.g., greater than 0 to 5 torr, greater than 0 to 2 torr, greater than 0 to 1 torr, greater than 0 to 0.75 torr, greater than 0 to 0.5 torr, greater than 0 to 0.25 torr, greater than 0 to 0.1 torr, greater than 0 to 0.075 torr, greater than 0 to 0.05 torr, greater than 0 to 0.025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.0075 torr, greater than 0 to 0. The gas is present in the environment at a partial pressure of 0.005 torr, greater than 0 to 0.0025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.00075 torr, greater than 0 to 0.0005 torr, greater than 0 to 0.00025 torr, greater than 0 to 0.0002 torr, greater than 0 to 0.0001 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. Exemplary ranges that may be considered as upper and lower limits for the partial pressure of water vapor include 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints.

[0069] Without being bound by theory, increasing the size of the solid composition increases the amount of water vapor that can be tolerated in the environment. In fact, without being bound by theory, the partial pressure of water vapor can increase linearly with increasing mass of the solid composition while maintaining substantially the same oxidation percentage (assuming the chambers 105 in which each of these comparative sublimation / distillation events occur have the same volume). As an example, in a chamber 105 with a volume of 1 cubic foot, approximately 5% of 1 g of the solid composition will be Yb oxide or Yb hydroxide and H gas due to oxidation in an environment with a partial pressure of water vapor of approximately 0.1 torr at the start of the sublimation / distillation period, while approximately 5% of 10 g of the solid composition will be Yb oxide or Yb hydroxide and H gas due to oxidation in an environment with a partial pressure of water vapor of approximately 1.1 torr at the start of the sublimation / distillation period. Furthermore, without being bound by theory, changing the volume of chamber 105 changes the amount of water vapor that can be tolerated in the environment, and it may be desirable to decrease the relative partial pressure of water vapor as the volume of chamber 105 increases, and it may be desirable to increase the relative partial pressure of oxygen as the volume of chamber 105 decreases.

[0070] It is contemplated that water vapor may be present in any of the above ranges and values ​​for at least 50% of the sublimation / distillation period, e.g., at least 55% of the sublimation / distillation period, at least 60% of the sublimation / distillation period, at least 65% of the sublimation / distillation period, at least 70% of the sublimation / distillation period, at least 75% of the sublimation / distillation period, at least 80% of the sublimation / distillation period, at least 85% of the sublimation / distillation period, at least 90% of the sublimation / distillation period, at least 95% of the sublimation / distillation period, at least 96% of the sublimation / distillation period, at least 97% of the sublimation / distillation period, at least 98% of the sublimation / distillation period, at least 99% of the sublimation / distillation period, or at least the entire sublimation / distillation period.

[0071] In some embodiments, O gas is present in the environment and is at a partial pressure of 10 torr or less during the sublimation / distillation period, e.g., 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, 0.0 The partial pressure is present at a partial pressure of 0.05 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints. In other words, the O2 gas is maintained at a partial pressure in the range of greater than 0 to 10 torr during the sublimation / distillation period, for example, greater than 0 to 5 torr, greater than 0 to 2 torr, greater than 0 to 1 torr, greater than 0 to 0.75 torr, greater than 0 to 0.5 torr, greater than 0 to 0.25 torr, greater than 0 to 0.1 torr, greater than 0 to 0.075 torr, greater than 0 to 0.05 torr, greater than 0 to 0.025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.0075 torr, greater than 0 to 0. The gas is present in the environment at a partial pressure of 0.005 torr, greater than 0 to 0.0025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.00075 torr, greater than 0 to 0.0005 torr, greater than 0 to 0.00025 torr, greater than 0 to 0.0002 torr, greater than 0 to 0.0001 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. Exemplary ranges that may be considered as upper and lower limits for the partial pressure of O2 gas include 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints.It is further contemplated that O gas may be present in any of the above ranges and values ​​for at least 50% of the sublimation / distillation period, e.g., at least 55% of the sublimation / distillation period, at least 60% of the sublimation / distillation period, at least 65% of the sublimation / distillation period, at least 70% of the sublimation / distillation period, at least 75% of the sublimation / distillation period, at least 80% of the sublimation / distillation period, at least 85% of the sublimation / distillation period, at least 90% of the sublimation / distillation period, at least 95% of the sublimation / distillation period, at least 96% of the sublimation / distillation period, at least 97% of the sublimation / distillation period, at least 98% of the sublimation / distillation period, at least 99% of the sublimation / distillation period, or at least the entire sublimation / distillation period.

[0072] In some embodiments, CO2 gas is present in the environment and is maintained at a partial pressure of 10 torr or less during the sublimation / distillation period, e.g., 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. The partial pressure is at a partial pressure of 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints. In other words, the CO2 gas is maintained at a partial pressure in the range of greater than 0 to 10 torr during the sublimation / distillation period, for example, greater than 0 to 5 torr, greater than 0 to 2 torr, greater than 0 to 1 torr, greater than 0 to 0.75 torr, greater than 0 to 0.5 torr, greater than 0 to 0.25 torr, greater than 0 to 0.1 torr, greater than 0 to 0.075 torr, greater than 0 to 0.05 torr, greater than 0 to 0.025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.0075 torr, greater than 0 to 0 The environment is present at a partial pressure of 0.005 torr, greater than 0 to 0.0025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.00075 torr, greater than 0 to 0.0005 torr, greater than 0 to 0.00025 torr, greater than 0 to 0.0002 torr, greater than 0 to 0.0001 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. Exemplary ranges that may be considered as upper and lower limits for the partial pressure of CO2 gas include 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints.It is further contemplated that CO gas may be present within any of the above ranges and values ​​for at least 50% of the sublimation / distillation period, e.g., at least 55% of the sublimation / distillation period, at least 60% of the sublimation / distillation period, at least 65% of the sublimation / distillation period, at least 70% of the sublimation / distillation period, at least 75% of the sublimation / distillation period, at least 80% of the sublimation / distillation period, at least 85% of the sublimation / distillation period, at least 90% of the sublimation / distillation period, at least 95% of the sublimation / distillation period, at least 96% of the sublimation / distillation period, at least 97% of the sublimation / distillation period, at least 98% of the sublimation / distillation period, at least 99% of the sublimation / distillation period, or at least the entire sublimation / distillation period.

[0073] In some embodiments, NO2 gas is present in the environment and is maintained at a partial pressure of 10 torr or less during the sublimation / distillation period, e.g., 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. The partial pressure is at a partial pressure of 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints. In other words, the NO2 gas is maintained at a partial pressure in the range of greater than 0 to 10 torr during the sublimation / distillation period, for example, greater than 0 to 5 torr, greater than 0 to 2 torr, greater than 0 to 1 torr, greater than 0 to 0.75 torr, greater than 0 to 0.5 torr, greater than 0 to 0.25 torr, greater than 0 to 0.1 torr, greater than 0 to 0.075 torr, greater than 0 to 0.05 torr, greater than 0 to 0.025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.0075 torr, greater than 0 to 0 The environment is present at a partial pressure of 0.005 torr, greater than 0 to 0.0025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.00075 torr, greater than 0 to 0.0005 torr, greater than 0 to 0.00025 torr, greater than 0 to 0.0002 torr, greater than 0 to 0.0001 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. Exemplary ranges that may be considered as upper and lower limits for the partial pressure of NO2 gas include 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints.It is further contemplated that NO gas is present within any of the above ranges and values ​​for at least 50% of the sublimation / distillation period, e.g., at least 55% of the sublimation / distillation period, at least 60% of the sublimation / distillation period, at least 65% of the sublimation / distillation period, at least 70% of the sublimation / distillation period, at least 75% of the sublimation / distillation period, at least 80% of the sublimation / distillation period, at least 85% of the sublimation / distillation period, at least 90% of the sublimation / distillation period, at least 95% of the sublimation / distillation period, at least 96% of the sublimation / distillation period, at least 97% of the sublimation / distillation period, at least 98% of the sublimation / distillation period, at least 99% of the sublimation / distillation period, or at least the entire sublimation / distillation period.

[0074] In some embodiments, CO gas is present in the environment and is at a partial pressure of 10 torr or less during the sublimation / distillation period, e.g., 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, 0.0 The partial pressure is present at a partial pressure of 0.05 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints. In other words, the CO gas is maintained at a partial pressure in the range of greater than 0 to 10 torr during the sublimation / distillation period, e.g., greater than 0 to 5 torr, greater than 0 to 2 torr, greater than 0 to 1 torr, greater than 0 to 0.75 torr, greater than 0 to 0.5 torr, greater than 0 to 0.25 torr, greater than 0 to 0.1 torr, greater than 0 to 0.075 torr, greater than 0 to 0.05 torr, greater than 0 to 0.025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.0075 torr, greater than 0 to 0. The gas is present in the environment at a partial pressure of 0.005 torr, greater than 0 to 0.0025 torr, greater than 0 to 0.002 torr, greater than 0 to 0.001 torr, greater than 0 to 0.00075 torr, greater than 0 to 0.0005 torr, greater than 0 to 0.00025 torr, greater than 0 to 0.0002 torr, greater than 0 to 0.0001 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. Exemplary ranges that may be considered as upper and lower limits for the partial pressure of CO gas include 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 having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints.It is further contemplated that CO gas is present within any of the above ranges and values ​​for at least 50% of the sublimation / distillation period, e.g., at least 55% of the sublimation / distillation period, at least 60% of the sublimation / distillation period, at least 65% of the sublimation / distillation period, at least 70% of the sublimation / distillation period, at least 75% of the sublimation / distillation period, at least 80% of the sublimation / distillation period, at least 85% of the sublimation / distillation period, at least 90% of the sublimation / distillation period, at least 95% of the sublimation / distillation period, at least 96% of the sublimation / distillation period, at least 97% of the sublimation / distillation period, at least 98% of the sublimation / distillation period, at least 99% of the sublimation / distillation period, or at least the entire sublimation / distillation period.

[0075] In some embodiments, one or more oxygen-containing gases are present in the environment and the total partial 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 period, e.g., 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 having any two of these values ​​as endpoints or any value within a range having any two of these values ​​as endpoints. In other words, the total partial pressure of the one or more oxygen-containing gases present in the environment during the sublimation / distillation period is in the range of from greater than 0 to 50 torr, e.g., from greater than 0 to 40 torr, from greater than 0 to 30 torr, from greater than 0 to 25 torr, from greater than 0 to 15 torr, from greater than 0 to 10 torr, from greater than 0 to 7.5 torr, from greater than 0 to 5 torr, from greater than 0 to 2.5 torr, from greater than 0 to 2 torr, from greater than 0 to 1 torr, from greater than 0 to 0.75 torr, from greater than 0 to 0.5 torr, from greater than 0 to 0.25 torr, from greater than 0 to 0.2 torr, from greater than 0 to 0.1 torr, from greater than 0 to 0.075 torr, from greater than 0 to 0.05 torr, from greater than 0 to 0.025 torr, from greater than 0 to 0.02 torr, from greater than 0 to 0.01 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. Exemplary ranges that may be considered as upper and lower limits for the partial pressure of one or more oxygen-containing gases include 0.001 torr to 50 torr, 0.001 torr to 30 torr, 0.001 torr to 25 torr, 0.001 torr to 10 torr, 0.001 torr to 5 torr, 0.001 torr to 1 torr, 0.01 torr to 50 torr, 0.01 torr to 25 torr, 0.01 torr to 10 torr, 0.01 torr to 5 torr, 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.

[0076] The one or more oxygen-containing gases present in the environment include one or more of water vapor, O gas, CO gas, NO gas, CO gas, hydrocarbon gases (including methane), and alcohol gases (including methanol, ethanol, and isopropyl alcohol). Further, it is contemplated that the one or more oxygen-containing gases are present in any of the above ranges and values ​​for at least 50% of the sublimation / distillation period, e.g., at least 55% of the sublimation / distillation period, at least 60% of the sublimation / distillation period, at least 65% of the sublimation / distillation period, at least 70% of the sublimation / distillation period, at least 75% of the sublimation / distillation period, at least 80% of the sublimation / distillation period, at least 85% of the sublimation / distillation period, at least 90% of the sublimation / distillation period, at least 95% of the sublimation / distillation period, at least 96% of the sublimation / distillation period, at least 97% of the sublimation / distillation period, at least 98% of the sublimation / distillation period, at least 99% of the sublimation / distillation period, or at least the entire sublimation / distillation period.

[0077] As noted above, by minimizing the level of oxygen-containing gas in the environment, oxidation is minimized during the sublimation / distillation process, allowing for an increase in the overall pressure in the environment when compared to previous techniques for sublimation / distillation of rare earth elements. Higher overall pressure allows more heated gas to come into contact with the solid composition, which may allow for faster and more complete sublimation / distillation by improving heat transfer to the material being sublimated / distilled. For example, by limiting the level of oxygen-containing gas in the environment to 10 torr or less, 1 torr or less, or any of the values ​​and ranges considered above, the overall pressure in the environment can be increased to 1 torr or more, 2 torr or more, 5 torr or more, 10 torr or more, 25 torr or more, 50 torr or more, 100 torr or more, 250 torr or more, 500 torr or more, 760 torr or more, 1000 torr or more, and 1520 torr or more, 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, while still minimizing oxidation. Higher overall pressures can also allow for simpler, more cost-effective designs that can be implemented without pressure / vacuum vessels and expensive vacuum equipment. Higher overall pressures can allow for more efficient transport of gas-phase Yb to surfaces (e.g., collection surfaces) located outside the line of sight of the heated surface, thereby enabling a more convoluted flow path, which is useful for increasing the yield of lutetium and increasing the separation ratio between ytterbium and lutetium. These increased overall pressures can be achieved by introducing non-reactive gases such as argon, krypton, xenon, or neon into chamber 105 and / or by introducing gases that are reactive but do not react with ytterbium or lutetium and that are not oxygen-containing, such as hydrogen gas.

[0078] 1 and 2, the temperature for sublimation and / or distillation (e.g., the temperature in the environment) may range from 400°C to 2000°C, e.g., 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 69 ...95°C, 450°C to 685°C, 450 The temperature may be in the range of 470°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, over 800°C to 2000°C, 1000°C to 2000°C, 1200°C to 2000°C, 1500°C to 2000°C, or any range having any two of these values ​​as endpoints. In practice, temperatures for sublimation and / or distillation (e.g., temperatures in the environment) may 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, 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. Also, according to various embodiments, the pressure of the environment at any of the above temperatures and temperature ranges may be between 2000 torr and 1×10 -8 torr, 1520 torr ~ 1 × 10 -8 torr, 1000 torr to 1×10 -8 torr, 760 torr to 1×10 -8 torr, 700 torr to 1×10 -8 torr, 500 torr to 1×10 -8 torr, 250 torr to 1×10 -7 torr, 100 torr to 1×10-6 torr, 1 torr to 1 × 10 -6 torr, 1×10 -1 torr~1×10 -6 torr, 1×10 -3 below torr, 1×10 -5 below torr, 1×10 -6 torr or less, 2000 torr to 1×10 -1 torr, 1520 torr to 1 torr, 1000 torr to 1 torr, 760 torr to 1 torr, 760 torr to 250 torr, any range having any two of these values ​​as endpoints, or any value within a range having any two of these values ​​as endpoints.

[0079] The time required for the sublimation and / or distillation step (e.g., sublimation / distillation duration) can vary widely and depends on the amount of material in the solid composition, the temperature, and the pressure. It can vary from 1 second to 1 week. In some embodiments, the time involved is the rate of sublimation or distillation, which in some embodiments can be from 10 min / g to 100 min / g of solid composition, or from 20 min / g to 60 min / g of solid composition. In one embodiment, the rate can be 40 min / g of solid composition.

[0080] Referring again to Figures 1 and 2, the process for initial purification by distillation and / or sublimation generally proceeds as follows: An enriched Yb-176 metal target is loaded into a tube with sealable ends. For example, the tube may be a quartz tube, which may have a diameter ranging from 0.5 cm to 2 cm, such as a 1 cm diameter. The tube is then sealed in an overpack (e.g., aluminum) suitable for irradiation and impermeable to water and air. The sealed overpack is irradiated, for example, by a reactor or other neutron source for several hours to several days (depending on the flux and batch requirements) to produce Lu-177 in the Yb-176 target. The sealed overpack is then loaded into a processing hot cell or isolator. Within the hot cell or isolator, which may include an inert environment, the irradiated Yb metal target is removed and placed inside a crucible 190, which is then placed into the vacuum chamber of the sublimation / distillation apparatus 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, or Ar, may be introduced into the environment to replace the partial pressure of the oxygen-containing gas. Additionally, or alternatively, the pressure in the environment may be reduced to reduce the partial pressure of all gases in the environment, including the oxygen-containing gas.

[0081] The crucible 190 is then heated, for example, to a first temperature using the heating element 170, for example, by radio frequency (RF) induction. At the first temperature, direct sublimation of Yb is indicated by a slight pressure increase within the vacuum chamber due to the designed leak path for the small amount of Yb vapor. As Yb metal sublimes from the heated crucible, it is deposited on a collection surface, where it can be actively cooled for collection and reuse. Sublimation continues for 30-50 minutes per gram of starting material (e.g., about 40 minutes per gram of starting material), and completion of the process takes approximately 5×10 -6 torr to approximately 1×10 -6 It is identified by a sudden drop in vacuum pressure below torr, or a drop in the H2 signal below the H2 gas threshold level.

[0082] As sublimation progresses or after sublimation is complete, crucible 190 can be heated to a second temperature higher than the first temperature. At this stage of the process, the produced lutetium or lutetium oxide, trace amounts of ytterbium or ytterbium oxide, and trace amounts of contaminants remain in crucible 190. Once crucible 190 has cooled to a threshold temperature, e.g., 90°C or less, the contents of the crucible, including the lutetium, are dissolved in acid for removal from the crucible and transfer to a chromatographic separation device. Crucible 190 can be cooled passively (e.g., by removing heat from heating element 170 and waiting a predetermined period of time for a certain thermal condition to occur) or actively (e.g., using a flowing gas or liquid).

[0083] Any of the above lutetium compositions or lutetium-enriched samples as described herein may be subjected to chromatographic separation to further concentrate lutetium in the composition or sample. Such chromatographic separation may include column chromatography, plate chromatography, thin cell chromatography, or high performance liquid chromatography. Exemplary processes for the purification of lutetium are those described in U.S. Patent Nos. 7,244,403 and 9,816,156, both of which are incorporated herein by reference in their entireties. However, it should be understood that other chromatographic separation techniques may be used to further concentrate lutetium separated using the techniques described herein. In one aspect, the process may include dissolving the lutetium and ytterbium compositions remaining in the crucible after sublimation in an acid and applying the resulting solution to a chromatography column or plate. This may include plate chromatography material, chromatography columns, HPLC chromatography columns, ion exchange columns, and the like.

[0084] As an illustrative example, a solution of lutetium in dilute HCl (i.e., 0.01-5N HCl) can be prepared. This can be applied to a solution-packed or dry ion exchange column, and the lutetium can be eluted by a further wash of dilute HCl. This is outlined in U.S. Pat. No. 7,244,403, where the solution affected by the treatment is generally a dilute solution of a strong acid, usually HCl. The resin bed can be in the form of a strong anion exchange resin in a column, and contact occurs by flowing the solution through the column. In some embodiments, the resin is a strong base anion exchange resin that is approximately 8% cross-linked. First, an HCl solution is flowed through the column to form an HCl-treated column, then a NaCl solution is flowed through the HCl-treated column to form a NaCl-treated column, and then sterile water is flowed through the NaCl-treated column. These preparation steps aid in eluting a sterile, non-pyrogenic product. The resin can then be dried prior to application of the lutetium solution. In some embodiments, the anion exchange resin is in powder form, generally with particles sized between 100 mesh and 200 mesh. To speed up the flow of the solution through the column, a sterile gas pressure can be applied to the head of the column. This can be done by injecting a sterile gas, preferably air, into the top of the column to push the lutetium-177 solution through the column. The lutetium-177 recovered from such a process can be of higher purity than before column chromatography through an anion exchange column.

[0085] In another aspect, the process may involve the use of a cation exchange resin for the purification of lutetium from a composition that also contains ytterbium. As an illustrative example, and as outlined in U.S. Pat. No. 9,816,156, the method includes the steps of: loading a first column packed with a cation exchange material with a Lu / Yb mixture dissolved in a mineral acid; exchanging the protons of the cation exchange material for ammonium ions; and washing the cation exchange material of the first column with water using an NH4Cl solution. The outlet of the first column is connected to the inlet of a second column, also packed with a cation exchange material. A gradient of water and chelating agent, starting with 100% HO at the inlet of the first column and progressing to 0.2 M chelating agent, is then applied to the columns to elute lutetium from the first and second columns. Illustrative examples of chelating agents include, but are not limited to, α-hydroxyisobutyric acid [HIBA], citric acid, citrate, butyric acid, butyrate, EDTA, EGTA, and ammonium ions. The method further includes determining the radioactivity dose at the outlet of the second column to identify elution of the Lu-177 compound, and collecting the first Lu-177 eluate from the outlet of the second column in a container, followed by protonating the chelating agent to inactivate it for complex formation with Lu-177. The method may further include the steps of: loading a final column packed with a cation exchange material by continuously delivering the acidic lutetium eluate to the inlet of the final column; washing the chelating agent with dilute mineral acid at a concentration of less than about 0.1 M; removing traces of other metal ions from the lutetium solution by washing the cation exchange material of the final column with mineral acid at various concentrations ranging from 0.01 to 2.5 M; and eluting the Lu-177 ions from the final column with concentrated mineral acid at a concentration of about 1 M to 12 M. Finally, the eluate containing lutetium of higher purity than that applied to the column may be collected, and the solvent and mineral acid may be removed by evaporation.

[0086] In a further aspect, the process may include dissolving a lutetium and ytterbium composition or a lutetium-enriched sample in an acid to form a dissolved lutetium / ytterbium solution, adding a chelating agent to the dissolved lutetium / ytterbium solution and neutralizing with a base to form a chelated lutetium / ytterbium solution containing chelated lutetium and chelated ytterbium, chromatographically separating the chelated solution, collecting a purified chelated lutetium fraction, and dechelating the lutetium to obtain purified lutetium. The purified chelated lutetium fraction has a higher purity of lutetium than the purity of lutetium in the dissolved lutetium / ytterbium solution. Using such a chromatographic process, a high level of lutetium purity can be achieved. For example, the purified lutetium obtained after chromatographic separation and workup may contain greater than 99% isotopic purity of Lu-177, including greater than 99.9% pure, greater than 99.99% pure, greater than 99.999% pure, or greater than 99.9999% pure Lu-177.

[0087] Typically, an ytterbium metal or metal oxide target is irradiated to form Lu-177. The target is then dissolved in acid, a chelating agent is added, the solution is neutralized with base to form the chelated metal, chromatographic separation is performed, and the purified metal is decomplexed / dechelated from the chelating agent. However, due to the limitations of chromatography starting from an impurity source of lutetium (i.e., an irradiated ytterbium oxide target), even on a preparative scale, the efficiency of chromatography is low, and only a small fraction of purified lutetium is obtained in each chromatographic cycle. As discussed above, the use of purified lutetium after distillation / sublimation offers surprising benefits in producing higher purity rare earth metals, particularly lutetium, on a larger scale and in a shorter period of time than can be obtained by either distillation or chromatography alone.

[0088] The initial dissolution of lutetium in acid can be carried out using hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, peroxosulfuric acid, perchloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, or a mixture of any two or more thereof. The acid concentration can be from 0.01M to 6M, and / or the base concentration can be from 0.01M to 6M, including concentrations from 1M to 6M and 2M to 6M. A chelating agent is then added along with a base (e.g., lithium hydroxide, sodium hydroxide, potassium hydroxide, NH4OH, or an alkylammonium hydroxide) to neutralize the acid and produce chelated lutetium. Chelation 177 The Lu now contains other impurities. For example, it will contain Yb, and may contain K, Na, Ca, Fe, Al, Si, Ni, Cu, Pb, La, Ce, Lu (other than Lu-177), Eu, Sn, Er, and Tm. HPLC is then performed. HPLC can be performed on a suitable column and eluted with a suitable mobile phase, each of which can vary under different method development scenarios. By way of example, the column can be a cation exchange column, an anion exchange column, a reversed-phase C18 column, etc., and the mobile phase can be any that is determined to achieve elution.

[0089] For further purification, it is then chelated. 177 Lu is applied to a high-performance liquid chromatography (HPLC) system (a reversed-phase C18 column with 12-14% by volume of methanol) and then eluted from there with a higher purity than if applied to the column. 177 Acidification of Lu with HCl releases it from the chelator as the chloride salt.

[0090] The mobile phase can be aqueous-based or organic solvent-based. Illustrative examples include, but are not limited to, water, alcohols, alkanes, ethers, esters, acids, bases, and aromatics. In various embodiments, the mobile phase can include water, methanol / water, methanol / trifluoroacetic acid / water, and / or methanol mobile phases.

[0091] After HPLC purification of the chelated lutetium, a dechelation process is performed to obtain purified lutetium as a lutetium solution and / or ionic substance. In some embodiments, dechelation comprises contacting the purified chelated lutetium fraction with an acid that is hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, peroxosulfuric acid, perchloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, or a mixture of any two or more thereof. The acid may have a concentration of 0.01M to 6M, and / or the base may have a concentration of 0.01M to 6M, including concentrations of 1M to 6M and 2M to 6M.

[0092] As mentioned above, the process described herein can be used for the separation of lutetium and ytterbium. However, it may also be used to separate any rare earth and / or actinide metal with different boiling / sublimation points, followed by further purification using chromatographic separation in the presence of various chelating agents. 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 comprises the chromatographic separation of a rare earth element from a mixture of at least two metal ions, at least one of which is Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Pm, Sm, Sc, Tb, Tm, Yb, or Y.

[0093] As used herein, the words "approximately," "about," "substantially," and similar words are intended to have broad meanings consistent with common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. These words should be understood by those of ordinary skill in the art reviewing this disclosure to allow for the description of certain features described in the detailed description and claimed below without limiting the scope of those features to given precise numerical values ​​or idealized geometric configurations. Accordingly, these words should be interpreted as indicating that insubstantial or minor variations or modifications of the subject matter described in the detailed description and claimed below are considered to be within the scope of the disclosure as set forth in the subsequent claims.

[0094] As used herein, the term "coupled" and variations thereof mean that two members are joined to one another, either directly or indirectly. The joining can be static (e.g., permanent or fixed) or movable (e.g., removable or releasable). The joining can be achieved by two members being directly joined to one another, by two members being joined to one another using a separate intervening member and an additional intermediate member joined to one another, or by two members being joined to one another using an intervening member integrally formed with one of the two members as a single, unitary body. When "coupled" or variations thereof are modified by an additional term (e.g., directly coupled), the general definition of "coupled" given above is modified by the plain linguistic meaning of the additional term (e.g., "directly coupled" means joining of two members without any separate intervening member), resulting in a narrower definition than the general definition of "coupled" given above. The joining can be mechanical, electrical, optical, or fluid.

[0095] References to the location of elements herein (e.g., "top," "bottom," "upper," "lower") are used merely to describe the orientation of various elements in the drawings. It should be noted that the orientation of various elements may vary in other exemplary embodiments, and such variations are intended to be encompassed by the present disclosure.

[0096] Although the figures and detailed description may indicate a particular order of method steps, the order of the steps may differ from that shown and described unless specified otherwise. Also, two or more steps may be performed simultaneously or concurrently in parallel unless specified otherwise. Such variations may depend, for example, on the software and hardware selected and on the choice of the designer. All such variations are within the scope of this disclosure. Similarly, software implementations of the described methods may be realized using standard programming techniques with rule-based logic and other logic implementing the various connection, processing, comparison, and decision steps.

[0097] While particular 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. Moreover, although various aspects of the claimed subject matter have been described herein, such aspects need not be utilized in combination. It is therefore intended that the following claims cover all such changes and modifications that are within the scope of the claimed subject matter.

Claims

1. 1. A method for purifying lutetium, comprising the steps of:

1. A method comprising: sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature in the range of 400°C to 2000°C over a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in said solid composition, said environment comprising water vapor, said water vapor being present in said environment at a partial pressure of 1.5 torr or less during said sublimation / distillation period.

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

3. 10. The method of 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 period.

4. 10. The method of claim 1, wherein the solid composition is in the range of 0.5 g to 10 g at the start of the sublimation / distillation period.

5. 10. The method of claim 1, wherein the water vapor is present in the environment during the sublimation / distillation period at a partial pressure of between 0.001 torr and 1.5 torr.

6. The environment is as follows: O ２ gas present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation period. ２ gas, CO ２ CO gas present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation period. ２ gas, NO ２ NO gas present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation period. ２ Gas, and CO gas, present in the environment at a partial pressure of 1 torr or less during the sublimation / distillation period. The method of claim 1 , comprising one or more of:

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

8. During the sublimation or distillation of ytterbium from the solid composition, the residual gas analyzer measures H ２ detecting a gas; H at levels below the threshold level ２ after detecting the gas, reducing the temperature in the environment to 90°C or less; The method of claim 7 further comprising:

9. The threshold level is 0.1 ppm H ２ The method of claim 8 , comprising:

10. 1. A method for purifying lutetium, comprising the steps of:

1. A method comprising: sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature in the range of 400°C to 2000°C over a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in said solid composition, said environment comprising one or more oxygen-containing gases, said one or more oxygen-containing gases being present in said environment at a total partial pressure of 10 torr or less during said sublimation / distillation period.

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

12. 11. The method of claim 10, wherein the 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 period.

13. 11. The method of claim 10, wherein the total pressure in the environment is 10 torr or greater during the sublimation / distillation period.

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

15. The one or more oxygen-containing gases present in the environment may be water vapor, O ２ Gas, CO ２ Gas, No ２ The method of claim 10 , wherein the gas comprises one or more of a CO gas, a hydrocarbon gas, and an alcohol gas.

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

17. During the sublimation or distillation of ytterbium from the solid composition, the residual gas analyzer measures H ２ detecting a gas; H at levels below the threshold level ２ after detecting the gas, reducing the temperature in the environment to 90°C or less; 17. The method of claim 16 further comprising:

18. 1. A method for purifying lutetium, comprising the steps of: sublimating or distilling ytterbium from a solid composition comprising ytterbium and lutetium in an environment at a temperature ranging from 400°C to 2000°C for a sublimation / distillation period to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in said solid composition. Equipped with the environment comprises one or more oxygen-containing gases, the one or more oxygen-containing gases being present in the environment at a total partial pressure of 1.5 torr or less during the sublimation / distillation period; one of the one or more oxygen-containing gases comprises water vapor, the water vapor being present in the environment at a partial pressure of 1.5 torr or less during the sublimation / distillation period; The method wherein the total pressure within said environment is greater than or equal to 2 torr during said sublimation / distillation period.

19. During the sublimation or distillation of ytterbium from the solid composition, a residual gas analyzer measures H in the environment. ２ detecting a gas; H at levels below the threshold level ２ after detecting the gas, reducing the temperature in the environment to 90°C or less; 20. The method of claim 18 further comprising:

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

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