Patent Application
20230407434
The present disclosure is generally related to the reduction of rare earth metals from rare earth metal oxides. More particularly, it is related to the reduction of ytterbium metal from ytterbium metal oxide.
Lutetium-177 (Lu-177) is a radioisotope that is used in the treatment of neuro endocrine tumors, prostate, breast, renal, pancreatic, and other cancers. In the coming years, approximately 70,000 patients per year will need Lu-177 during their medical treatments. Some current techniques for isolating and purifying Lu-177 use ytterbium.
Accordingly, a need exists for improved techniques for isolating ytterbium metal, which may be used in the separation and purification of radioisotopes, such as Lu-177.
According to a first aspect of the present disclosure, a method includes forming a powder mixture from a rare earth oxide powder and a lanthanum powder, heating the powder mixture in a crucible assembly positioned in a reduced pressure environment, wherein heating the powder mixture comprises applying heat using a heating element and heating the powder mixture reduces the rare earth oxide powder into a rare earth metal that collects on a collection region of the crucible assembly. The method also includes monitoring a pressure in the reduced pressure environment using a pressure sensor and reducing the heat applied by the heating element to the powder mixture when the pressure in the reduced pressure environment is above a threshold pressure.
A second aspect includes the method of the first aspect, wherein the rare earth oxide powder comprises an ytterbium oxide powder or a gadolinium oxide powder and the rare earth metal comprises an ytterbium metal or a gadolinium metal.
A third aspect includes the method of the first or second aspects, further comprising halting application of heat by the heating element to the powder mixture when the pressure in the reduced pressure environment is above the threshold pressure.
A fourth aspect includes the method of any of the previous aspects, further comprising resuming application of heat from the heating element to the powder mixture when the pressure of the reduced pressure environment is at or below the threshold pressure.
A fifth aspect includes the method of any of the previous aspects, wherein the powder mixture is a homogeneous mixture of rare earth oxide powder and lanthanum powder.
A sixth aspect includes the method of any of the previous aspects, wherein heating the powder mixture retains lanthanum in a reaction region of the crucible assembly.
A seventh aspect includes the method of any of the previous aspects, further comprising cooling the collection region of the crucible assembly while heating powder mixture to promote collection of the rare earth metal on the collection region.
An eighth aspect includes the method of any of the previous aspects, wherein the threshold pressure is in a range of from 1×10−6 torr to 1×10−2 torr.
A ninth aspect includes the method of any of the previous aspects, wherein the heating element comprises an induction heating element.
A tenth aspect includes the method of any of the previous aspects, wherein when heating the powder mixture, the powder mixture is positioned in a reaction crucible of the crucible assembly, the crucible assembly further comprising a collection crucible, wherein the collection crucible is in the collection region of the crucible assembly.
An eleventh aspect includes the method of the tenth aspect, further comprising, when heating the powder mixture, cooling the collection crucible.
A twelfth aspect includes the method of the tenth aspect or eleventh aspect, wherein the crucible assembly further comprises a support sleeve and an insulative holder; the collection crucible extends into a first end of the support sleeve; and the reaction crucible extends into a first end of the insulative holder.
A thirteenth aspect includes the method of any of the tenth through twelfth aspects, wherein the support sleeve comprises graphite.
A fourteenth aspect includes the method of any of the tenth through thirteenth aspects, wherein the insulative holder comprises a ceramic material.
A fifteenth aspect includes the method of any of the tenth through fourteenth aspects, further comprising, when heating the powder mixture, cooling the collection crucible using a cold finger extending into a second end of the support sleeve and contacting the collection crucible.
A sixteenth aspect includes the method of any of the tenth through fifteenth aspects, wherein when heating the powder mixture, a stepper is coupled to a second end of the insulative holder, wherein the stepper is configured to translate the crucible assembly within the reduced pressure environment.
A seventeenth aspect includes the method of any of the tenth through sixteenth aspects, wherein the collection crucible is removably coupled to the reaction crucible by a collar.
An eighteenth aspect includes the method of the seventeenth aspect, wherein the collar comprises a refractory metal.
A nineteenth aspect includes the method of any of the tenth through eighteenth aspects, wherein the reaction crucible and the collection crucible each comprise a refractory metal.
A twentieth aspect includes the method of any of the tenth through nineteenth aspects, wherein an inner chamber of the reaction crucible faces an inner chamber of the collection crucible.
A twenty-first aspect includes the method of any of the previous aspects, further comprising orienting a collection substrate to face the collection region of the crucible assembly holding the rare earth metal; and sublimating the rare earth metal in an environment at a temperature in a range of from 400° C. to 3000° C. to transfer the rare earth metal from the collection region of the crucible assembly to a collection surface of the collection substrate, wherein the rare earth metal comprises an ytterbium metal.
A twenty-second aspect includes the method of the twenty-first aspect, further comprising removing the ytterbium metal from the collection substrate; and irradiating the ytterbium metal with neutrons to form an irradiated solid composition comprising ytterbium and lutetium.
A twenty-third aspect includes the method of the twenty-second aspect, further comprising sublimating ytterbium from the irradiated solid composition in an environment at a temperature in a range of from 400° C. to 3000° C. to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in the irradiated solid composition.
A twenty-fourth aspect includes the method of the twenty-third aspect, wherein the environment is an inert or reduced pressure environment.
A twenty-fifth aspect includes the method of the twenty-third or twenty-fourth aspects, wherein the temperature is less than 700° C.
A twenty-sixth aspect includes the method of any of the previous aspects, wherein the rare earth oxide powder comprises rare earth oxide particles comprising an average maximum cross-sectional dimension of 5 μm or less and a particle size distribution in which 90% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 10 μm or less.
According to a twenty-seventh aspect of the present disclosure, a method includes forming a powder mixture from a rare earth oxide powder and a lanthanum powder; wherein the rare earth oxide powder comprises rare earth oxide particles comprising an average maximum cross-sectional dimension of 5 μm or less and a particle size distribution in which 90% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 10 μm or less; agitating the powder mixture to increase a distribution uniformity of the rare earth oxide powder and the lanthanum powder in the powder mixture; and heating the powder mixture in a crucible assembly positioned in a reduced pressure environment, wherein heating the powder mixture reduces the rare earth oxide powder into a rare earth metal that collects on a collection region of the crucible assembly.
A twenty-eighth aspect includes the method of the twenty-seventh aspect, wherein, subsequent to agitating the powder mixture, the powder mixture comprises a homogeneous mixture of the rare earth oxide powder and the lanthanum powder.
A twenty-ninth aspect includes the method of the twenty-seventh or twenty-eighth aspects, wherein the rare earth oxide particles comprise an average maximum cross-sectional dimension of 3 μm or less.
A thirtieth aspect includes the method of any of the twenty-seventh through twenty-ninth aspects, wherein the rare earth oxide particles comprise an average maximum cross-sectional dimension in a range of 1 μm to 3 μm.
A thirty-first aspect includes the method of any of the twenty-seventh through thirtieth aspects, wherein the particle size distribution of the rare earth oxide powder is such that 95% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 10 μm or less.
A thirty-second aspect includes the method of any of the twenty-seventh through thirty-first aspects, wherein the particle size distribution of the rare earth oxide powder is such that 90% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 5 μm or less.
A thirty-third aspect includes the method of any of the twenty-seventh through thirty-second aspects, wherein the particle size distribution of the rare earth oxide powder is such that 95% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 5 μm or less.
A thirty-fourth aspect includes the method of any of the twenty-seventh through thirty-third aspects, wherein the lanthanum powder comprises lanthanum particles comprising an average maximum cross-sectional dimension of 90 μm or less.
A thirty-fifth aspect includes the method of any of the twenty-seventh through thirty-fourth aspects, wherein when heating the powder mixture, the crucible assembly is positioned in a reduced pressure environment.
A thirty-sixth aspect includes the method of any of the twenty-seventh through thirty-fifth aspects, further comprising, prior to agitating the powder mixture, positioning the powder mixture in a reaction crucible of the crucible assembly such that the powder mixture is agitated in the reaction crucible, and subsequent to agitating the powder mixture, packing the powder mixture to increase a density of the powder mixture in the reaction crucible.
A thirty-seventh aspect includes the method of any of the twenty-seventh through thirty-sixth aspects, further comprising, prior to forming the powder mixture, milling the rare earth oxide powder to increase a sphericity the rare earth oxide particles of the rare earth oxide powder.
A thirty-eighth aspect includes the method of the thirty-seventh aspect, wherein milling the rare earth oxide powder comprises jet milling the rare earth oxide powder.
A thirty-ninth aspect includes the method of the thirty-seventh or thirty-eighth aspects, wherein, subsequent to milling the rare earth oxide powder, the ratio of the maximum cross-sectional dimension to the minimum cross-sectional dimension of 90% of more of the rare earth oxide particles of the rare earth oxide powder is 2:1 or less.
A fortieth aspect includes the method of any of the thirty-seventh through the thirty-ninth aspects, wherein, subsequent to milling the rare earth oxide powder, the ratio of the maximum cross-sectional dimension to the minimum cross-sectional dimension of 90% of more of the rare earth oxide particles of the rare earth oxide powder is 1.5:1 or less.
A forty-first aspect includes the method of any of the twenty-seventh through fortieth aspects, wherein the ratio of the maximum cross-sectional dimension to the minimum cross-sectional dimension of 90% of more of the rare earth oxide particles of the rare earth oxide powder is 2:1 or less.
A forty-second aspect includes the method of any of the twenty-seventh through forty-first aspects, wherein the ratio of the maximum cross-sectional dimension to the minimum cross-sectional dimension of 90% of more of the rare earth oxide particles of the rare earth oxide powder is 1.5:1 or less.
A forty-third aspect includes the method of any of the twenty-seventh through forty-second aspects, wherein the rare earth oxide powder comprises an ytterbium oxide powder or a gadolinium oxide powder and the rare earth metal comprises an ytterbium metal or a gadolinium metal.
These and additional features provided by the embodiments described herein will be more fully understood in view of the following detailed description, in conjunction with the drawings.
The embodiments set forth in the drawings are illustrative and exemplary in nature and not intended to limit the subject matter defined by the claims. The following detailed description of the illustrative embodiments can be understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:
Referring generally to the figures, embodiments of the present disclosure are directed to methods of reducing rare earth oxides to rare earth metals. For example, embodiments of the present disclosure are directed to methods of reducing a rare earth oxide, such as ytterbium oxide, to a rare earth metal, such as ytterbium metal, in a crucible assembly. The crucible assembly may comprise a reaction crucible fluidly coupled to a collection crucible such the fluids, including gases, may flow between the reaction crucible and the collection crucible, for example, from the reaction crucible to the collection crucible. A powder mixture comprising a rare earth oxide powder, such as an ytterbium oxide powder, and a lanthanum powder may be heated in the crucible assembly positioned in a reduced pressure environment by applying heat to a reduction region of the crucible assembly using a heating element. Heating the powder mixture reduces the rare earth oxide powder into a rare earth metal that collects on a collection region of the crucible assembly. The efficiency and quality of the reduction process may be improved by operating within certain pressure and temperature ranges. The efficiency and quality of the reduction process may also be improved by increasing the distribution uniformity of the powder mixture, reducing the particle size of the rare earth oxide particles, and increasing a sphericity of the rare earth oxide particles. Without intending to be limited by theory, the reduction techniques described herein take an advantage of the large differences in vapor pressure between the produced rare-earth metal and the reductant, along with any potential by-products or other impurities. These vapor pressure differences also purify the reduced rare-earth metal by separating the reduced metal from the by-products and impurities. For example, the reduced rare-earth metal may have a purity of 99% or greater. The method described herein includes a pressure monitoring step to continuous or intermittently measure the pressure in the reduced pressure environment such that the heat applied to the powder mixture may be reduced and/or removed when the pressure in the reduced pressure environment is above a threshold pressure, such as a threshold pressure in a range of from 1×10−6 torr and 5×10−5 torr.
Ytterbium metal collected using methods and systems described herein may then be irradiated and thereafter processed to obtain high purity lutetium, for example high purity isotopes of lutetium, such as Lu-177. Lu-177 is useful for many medical applications, because during decay it emits a low energy beta particle that is suitable for treating tumors. It also emits two gamma rays that can be used for diagnostic testing. Isotopes with both treatment and diagnostic characteristics are termed “theranostic.” Not only is Lu-177 theranostic, but it also has a 6.65-day half-life, which allows for more complicated chemistries to be employed, as well as allowing for easy global distribution. Lu-177 also exhibits chemical properties that allow for binding to many bio molecules, for use in a wide variety of medical treatments. The processes described herein provide efficient and effective techniques for obtaining ytterbium metal from ytterbium oxide, which is easier to obtain than ytterbium metal, such that the ytterbium metal may be used to isolate isotopes of interest, such as Lu-177. Moreover, the technique described herein may be used to obtain other rare earth metals from their oxides, such as gadolinium, samarium, europium, and terbium.
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The sublimation/distillation system 10 further comprises one or more temperature sensors 11 and one or more pressure sensors 12. The one or more temperature sensors 11 are configured and positioned to monitor the temperature in the chamber 15, the temperature of the reaction crucible 110, and the temperature of the collection crucible 120. The one or more pressure sensors 12 are configured and positioned to monitor the pressure in the chamber 15 and the pressure within the reaction crucible 110, and the pressure within the collection crucible 120. Example temperature sensors 11 include thermocouples, resistive temperature detectors, thermopiles, thermistors, or any other known or yet to be developed temperature sensor. Example pressure sensors 12 include ion gauges, or any other known or yet to be developed pressure sensor suitable for measuring pressure levels below 1 torr.
Referring now to
It may be advantageous that the rare earth oxide particles of the rare earth oxide powder have a small maximum cross-sectional dimension (e.g., a small diameter) as this may increase the distribution uniformity of the powder mixture and increase the packing density of the powder mixture, both of which improve the efficiency of the reduction process, allowing more rare earth metal to be recovered, increasing yield. Indeed, packing the particles of the powder mixture more closely has the benefit of increasing surface area to make the reduction reaction proceed more completely, conserving the rare earth oxides, which may be quite valuable, as well as increasing the amount of material present during the reduction reaction, increasing yield and throughput.
In some embodiments, the rare earth oxide powder comprises rare earth oxide particles comprising an average maximum cross-sectional dimension of 8 μm or less, such as 7 μm or less, 6 μm or less, 5 μm or less, 4 μm or less, 3 μm or less, 4 μm or less, 2 μm or less, 1 μm or less, 0.5 μm or less, 0.1 μm or less, any range having any two of these values as endpoints, such as 0.5 μm to 5, 1 μm to 4 μm, and 1 μm to 3 μm, or any value in a range having any two of the values as endpoints. In some embodiments, the lanthanum powder comprises lanthanum particles comprising an average maximum cross-sectional dimension of 90 μm or less, such as 100 μm or less, such as 90 μm or less, 80 μm or less, 70 μm or less, 60 μm or less, 50 μm or less, or any range having any two of these values as endpoints or any value in a range having any two of the values as endpoints.
It may also be advantageous that the rare earth oxide particles of the rare earth oxide powder have a particle size distribution in which most of the rare earth oxide particles have a small maximum cross-sectional dimension (e.g., a small diameter) as this may increase the distribution uniformity of the powder mixture and increase the packing density of the powder mixture, both of which improve the efficiency of the reduction process, allowing more rare earth metal to be recovered, increasing yield. In some embodiments, the rare earth oxide particles of the rare earth oxide powder comprise a particle size distribution in which 90% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 10 μm or less. In some embodiments, the rare earth oxide particles of the rare earth oxide powder comprise a particle size distribution in which 95% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 10 μm or less. In some embodiments, the rare earth oxide particles of the rare earth oxide powder comprise a particle size distribution in which 99% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 10 μm or less. In some embodiments, the rare earth oxide particles of the rare earth oxide powder comprise a particle size distribution in which 90% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 5 μm or less. In some embodiments, the rare earth oxide particles of the rare earth oxide powder comprise a particle size distribution in which 95% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 5 μm or less. In some embodiments, the rare earth oxide particles of the rare earth oxide powder comprise a particle size distribution in which 99% or more of the rare earth oxide particles comprise a maximum cross-sectional dimension of 5 μm or less.
Moreover, it may be advantageous of the rare earth oxide particles to have a high sphericity to improve packing efficiency of the powder mixture and improve the efficiency of the reduction process, allowing more rare earth metal to be recovered, increasing yield. Indeed, in some embodiments, the ratio of the maximum cross-sectional dimension to the minimum cross-sectional dimension of 90% of more of the rare earth oxide particles of the rare earth oxide powder may be 2.5:1 or less, for example, 2.4:1 or less, 2.5:1 or less, 2.2:1 or less, 2.1:1 or less, 2:1 or less, 1.9:1 or less, 1.8:1 or less, 1.7:1 or less, 1.6:1 or less, 1.5:1 or less, 1.4:1 or less, 1.3:1 or less, 1.2:1 or less, 1.1:1 or less, or any range having any two of these values as endpoints or any value in a range having any two of the values as endpoints. Moreover, in some embodiments, the ratio of the maximum cross-sectional dimension to the minimum cross-sectional dimension of 95% of more of the rare earth oxide particles of the rare earth oxide powder may be 2.5:1 or less, for example, 2.4:1 or less, 2.5:1 or less, 2.2:1 or less, 2.1:1 or less, 2:1 or less, 1.9:1 or less, 1.8:1 or less, 1.7:1 or less, 1.6:1 or less, 1.5:1 or less, 1.4:1 or less, 1.3:1 or less, 1.2:1 or less, 1.1:1 or less, or any range having any two of these values as endpoints or any value in a range having any two of the values as endpoints. The method may include a milling step, which can help achieve the desired sphericity. For example, prior to forming the powder mixture, the method may comprise milling the rare earth oxide powder, for example, jet milling the rare earth oxide powder, to increase a sphericity the rare earth oxide particles of the rare earth oxide powder. This may also increase a volume to surface area ratio of the rare earth oxide particles. It should be understood that any suitable milling technique may be used.
In some embodiments, the powder mixture is a homogeneous mixture of rare earth oxide powder (e.g., ytterbium oxide powder or gadolinium powder) and lanthanum powder. To form a homogenous mixture, the rare earth oxide powder and lanthanum powder may be mixed until the powder mixture is homogenous grey. In some embodiments, the powder mixture comprises rare earth oxide powder and a range of from 15% to 250% excess (by mole) lanthanum metal powder, for example, from 25% to 200% excess (by mole), from 50% to 200% excess (by mole), from 75% to 200% excess (by mole), from 90% to 200% excess (by mole), from 100% to 200% excess (by mole), from 125% to 200% excess (by mole), from 150% to 200% excess (by mole), from 175% to 200% excess (by mole), any range having any two of these values as endpoints, or any value in a range having any two of these values as endpoints. The powder mixture may be positioned in the reaction region 102 of the crucible assembly 100, for example, in the reaction crucible 110.
In some embodiments, the method further comprises agitating the powder mixture to increase a distribution uniformity of the rare earth oxide powder and the lanthanum powder in the powder mixture. Agitating the powder mixture may comprising mixing, shaking, or the like. The agitating step may occur while the powder mixture is in the reaction crucible 110. In some embodiments, the powder mixture is a homogeneous mixture after agitating the powder mixture. Next, the method may comprise packing the powder mixture to increase a density of the powder mixture in the reaction crucible 110, for example, by stamping the powder mixture to press the particles of the power mixture together.
Next, the crucible assembly 100 housing the powder mixture may be placed in the chamber 15 of the sublimation/distillation system 10, which forms a reduced pressure environment. The method further comprises heating the powder mixture by applying heat to the reaction crucible 110 using the heating element 25, and thus applying heat to the powder mixture. Heating the powder mixture reduces the ytterbium oxide powder into an ytterbium metal that collects on the collection region 104 of the crucible assembly 100, for example, in the collection crucible 120. As heat is applied to the powder mixture, ytterbium metal may sublimate from the powder mixture, separating from the ytterbium oxide, lanthanum, and lanthanum oxide, and collecting in the collection crucible 120. In contrast to the ytterbium oxide, lanthanum is retained in the reaction region 102 of the crucible assembly 100, for example, in the reaction crucible 110, as heat is applied to the powder mixture. Thus, the ytterbium metal is separated from both the oxygen of the ytterbium oxide and from the lanthanum of the powder mixture. In some embodiments, the powder mixture is heated to a temperature less than 900° C., for example, in a range of from 200° C. to less than 900° C. or 300° C. to 875° C., for example, a temperature of 300° C., 350° C., 400° C., 450° C., 500° C., 550° C., 600° C., 650° C., 700° C., 750° C., 800° C., 825° C., 850° C., 875° C., 890° C., or value in a range having any two of these values as endpoints.
In some embodiments, the collection region 104 of the crucible assembly 100, for example, the collection crucible 120, may be cooled while the powder mixture is heated. This cooling promotes collection of the ytterbium metal in the collection crucible 120. For example, in some embodiments, the sublimation/distillation system 10 includes a cold finger, which may be actively cooled using one or more cooling fluid lines, and the cold finger extends into the second end 146 of the support sleeve 140 to cool the collection crucible 120. In some embodiments, the cold finger may directly contact the collection crucible 120. Moreover, in some embodiments, a stepper may be coupled to the second end 136 of the insulative holder 130 when heating the powder mixture. The stepper is configured to translate the crucible assembly 100 within the reduced pressure environment (e.g., within the chamber 15 of the sublimation/distillation system 10) facilitating selective positioning of the crucible assembly 100, for example, with respect to the heating element 25.
Referring still to
Reducing the temperature when the pressure in the reduced pressure environment is above the threshold pressure improves the operational effectiveness and efficiency of the rare earth oxide reduction process. Maintaining the variables of temperature and pressure within desired ranges allows the underlying chemical processes to be better understood and controlled, facilitating increases in process scale (e.g., increases in the volume of rare earth oxides reduced in the process). Moreover, reducing the temperature when the pressure in the reduced pressure environment both improves the purity of the collected rare earth metal and minimizes loss of the rare earth metal. For example, an increase in pressure in the crucible assembly 100 may occur due to gaseous rare earth metal (such as gaseous ytterbium metal) escaping the crucible assembly 100, lowering the yield. Reducing temperature when the pressure is above the threshold pressure temporarily slows the reduction reaction, temporarily reducing the amount of newly reduced rare earth metal that may escape from the crucible assembly 100 until the pressure is below the threshold pressure and the crucible assembly 100 is in a condition in which minimal gaseous rare earth metal is lost.
In some embodiments, the reduction process is complete when the pressure is at or below the threshold pressure, the heating element continues to apply heat to the crucible assembly, and the temperature of the reaction region 102 of the crucible assembly 100 (e.g., the reaction crucible 110) is greater than 1000° C. These parameters indicate that substantially all sublimate-able material has vaporized, and nothing else is vaporizing at appreciable rates. For example, these parameters may be achieved if, for example, all the lanthanum has reacted, leaving no reductant for the reaction. Once these parameters are reached, the method may include removing the application of heat to the reaction region 102 of the crucible assembly 100 (e.g., the reaction crucible 110), allowing the temperature to reduce and the ytterbium metal to be collected.
After separating ytterbium metal from the powder mixture, the method may next comprise collecting the ytterbium metal. One way to collect the ytterbium metal is by performing an additional sublimation step to transfer the ytterbium metal from the collection region 104 of the crucible assembly 100 (e.g., from the collection crucible 120) to a collection substrate comprising a material and shape that facilitates removal and collection of the ytterbium metal. One example collection substrate is a flat quartz plate. Other example collection substrates include molybdenum, titanium, and tantalum substrates, for example, a flat molybdenum plate, a flat titanium plate, or a flat tantalum plate. This method step may comprise orienting a collection substrate to face the collection region 104 of the crucible assembly 100, which is now holding the ytterbium metal (e.g., orienting the collection substrate to face an open end of the collection crucible 120) and sublimating the ytterbium metal in an environment at a temperature in a range of from 400° C. to 3000° C. to transfer the ytterbium metal from the collection region 104 of the crucible assembly 100 to a collection surface of the collection substrate. The ytterbium metal may then be removed from the collection substrate for further processing. Once the ytterbium metal is collected (e.g., removed from the collection substrate), the method may next comprise irradiating the ytterbium metal with neutrons to form an irradiated solid composition comprising ytterbium and lutetium. This irradiation step may occur using a nuclear reactor, a particle accelerator, or any other known or yet to be developed source of neutrons.
In some embodiments, lutetium may be separated and purified from the irradiated solid composition, for example, using the methods described in PCT/US2020/061332 and PCT/US2021/025439, both of which are incorporated herein by reference in their entirety. For example, ytterbium may be sublimated from the irradiated solid composition in an environment at a temperature in a range of from 400° C. to 3000° C. to leave a lutetium composition comprising a higher weight percentage of lutetium than was present in the irradiated solid composition. The environment may be a reduced pressure environment and/or an inert environment. In some embodiments, the temperature in the environment is less than 700° C.
The vaporized fraction of the irradiated solid composition can then be recovered downstream after the vapor is condensed. In this case, the ytterbium is vaporized (and it may be collected downstream for later use) leaving behind a material that is enriched in lutetium. This may be conducted on a large scale, increasing the amount of lutetium available. It is noted that the ytterbium that is collected is available for recycling (e.g., for another round of neutron irradiation) to produce further irradiated solid composition and to thereafter produce further lutetium in subsequent runs of the process. The ytterbium that is sublimated/distilled from the solid composition may be recycled as additional target material for irradiation and re-use in a subsequent separation process.
The sublimation/distillation process of separating ytterbium from the irradiated solid composition (“the lutetium yielding sublimation”) yields a sample (“the lutetium composition”) that is enriched in lutetium as compared to the irradiated solid composition that enters the process. The yields and purity may be measured in a number of ways. For example, in some embodiments, the process yields an ytterbium mass reduction of the solid composition from 1000:1 to 10,000:1. In other words, after the lutetium yielding sublimation 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 the lutetium composition that is recovered there may, in some embodiments, be from 1 wt % to 90 wt % of ytterbium relative to total remaining mass that will then be separated as described below in a chromatographic process. In other embodiments, the ytterbium that is collected from the lutetium yielding sublimation is collected in an amount that is from 90 wt % to 99.999 wt % of the ytterbium present in the solid composition. The purification steps are also conducted 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. Stated another way, the lutetium yielding sublimation includes subjecting a sample comprising Yb-176 and Lu-177 to sublimation, distillation, or a combination thereof to remove at least a portion of the Yb-176 from the sample and form a Lu-177-enriched sample.
The temperature for the lutetium yielding sublimation (e.g., the temperature in the environment) may be in a range of from 400° C. to 3000° C., for example, from 450° C. to 1500° C., from 450° C. to 1200° C., from 450° C. to 1000° C., from 400° C. to 1000° C., from 400° C. to 900° C., from 400° C. to 800° C., from 450° C. to 700° C., from 400° C. to less than 700° C., from 400° C. to 695° C., from 450° C. to 690° C., from 450° C. to 685° C., from 450° C. to 680° C., from 450° C. to 675° C., from 450° C. to 670° C., from 450° C. to 665° C., from 450° C. to 660° C., from 450° C. to 655° C., from 450° C. to 650° C., from 450° C. to 645° C., from 450° C. to 640° C., from 450° C. to 635° C., from 450° C. to 630° C., from 450° C. to 625° C., 470° C. to about 630° C., from 800° C. to 3000° C., from greater than 800° C. to 3000° C., from 1000° C. to 3000° C., from 1200° C. to 3000° C., from 1500° C. to 3000° C., or any range having any two of these values as endpoints. Indeed, the temperature for sublimation and/or distillation (e.g., the temperature 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., 2100° C., 2200° C., 2300° C., 2400° C., 2500° C., 2600° C., 2700° C., 2800° C., 2900° C., 3000° C., any range having any two of these values as endpoints, or any value in a range having any two of these values as endpoints. Also, according to various embodiments, the pressure of the environment at any of the temperatures and temperature ranges described above may be in a range of from 2000 torr to 1×10−8, from 1520 torr to 1×10−8 torr, from 1000 torr to 1×10−8 torr, from 760 torr to 1×10−8 torr, from 700 torr to 1×10−8 torr, from 500 torr to 1×10−8 torr, from 250 torr to 1×10−7 torr, from 100 torr to 1×10−6 torr, from 1 torr to 1×10−6 torr, from 1×10−1 torr to 1×10−6 torr, 1×10−3 or less, 1×10−5 torr or less, 1×10−6 torr or less, from 2000 torr to 1×10−1 torr, from 1520 torr to 1 torr, from 1000 torr to 1 torr, from 760 torr to 1 torr, from 760 torr to 250 torr, any range having any two of these values as endpoints, or any value in a range having any two of these values as endpoints.
In some embodiments, temperature ramp rates over a period of 10 minutes to 2 hours may be employed to ensure no blistering or uneven heating of the irradiated solid composition. In some embodiments, prior to heating, a vacuum is established to degas the sample. This vacuum may be about 1×10−6 torr for approximately 5 minutes to 1 hour. The time period required for the lutetium yielding sublimation may vary widely and is dependent upon the amount of material in the irradiated solid composition, the temperature, and the pressure. It may vary from 1 second to 1 week. In some embodiments, it is a rate of sublimation or distillation that is pertinent to the question of time. It may, in some embodiments, be at a rate of 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 may be 40 min/g of solid composition.
It has been observed that a purification of greater than 1000:1 reduction (i.e. a 1000 times reduction in the amount of Yb present) in Yb may be achieved. This includes greater than approximately 3000:1, greater than 8000:1, greater than 10,000:1, up to and including approximately 40,000:1. However, higher reductions in Yb may be required to meet purity requirements for some pharmaceutical products. Accordingly, additional purification may be conducted prior to use in pharmaceutical applications. Such purification may be obtained through the use of chelators and/or chromatographic separation.
Any of the above lutetium compositions or lutetium-enriched samples, as described herein, may be subjected to chromatographic separation to further enrich the lutetium in the composition or sample. Such chromatographic separations may include column chromatography, plate chromatography, thin cell chromatography, or high-performance liquid chromatography. Illustrative processes for purification of lutetium may be as described in U.S. Pat. Nos. 7,244,403 and 9,816,156, both of which are incorporated herein by reference in their entirety. However, it should be understood that other chromatographic separation techniques may be used to further enrich the lutetium separated using the techniques described herein. In one aspect, a process may include dissolving in an acid the lutetium and ytterbium composition that remains after sublimation and applying the resultant solution to a chromatographic column or plate. This may include plate chromatographic materials, chromatographic columns, HPLC chromatographic columns, ion exchange columns, and the like.
As utilized herein, the terms “approximately,” “about,” “substantially”, and similar terms are intended to have a broad meaning in harmony with the common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to the precise numerical values or idealized geometric forms provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the disclosure as recited in the appended claims.
The term “coupled” and variations thereof, as used herein, means the joining of two members directly or indirectly to one another. Such joining may be stationary (e.g., permanent or fixed) or moveable (e.g., removable or releasable). Such joining may be achieved with the two members coupled directly to each other, with the two members coupled to each other using a separate intervening member and any additional intermediate members coupled with one another, or with the two members coupled to each other using an intervening member that is integrally formed as a single unitary body with one of the two members. If “coupled” or variations thereof are modified by an additional term (e.g., directly coupled), the generic definition of “coupled” provided above is modified by the plain language meaning of the additional term (e.g., “directly coupled” means the joining of two members without any separate intervening member), resulting in a narrower definition than the generic definition of “coupled” provided above. Such coupling may be mechanical, electrical, optical, or fluidic.
References herein to the positions of elements (e.g., “top,” “bottom,” “above,” “below”) are merely used to describe the orientation of various elements in the FIGURES. It should be noted that the orientation of various elements may differ according to other exemplary embodiments, and that such variations are intended to be encompassed by the present disclosure.
Although the figures and description may illustrate a specific order of method steps, the order of such steps may differ from what is depicted and described, unless specified differently above. Also, two or more steps may be performed concurrently or with partial concurrence, unless specified differently above. Such variation may depend, for example, on the software and hardware systems chosen and on designer choice. All such variations are within the scope of the disclosure. Likewise, software implementations of the described methods could be accomplished with standard programming techniques with rule-based logic and other logic to accomplish the various connection steps, processing steps, comparison steps, and decision steps.
While particular embodiments have been illustrated and described herein, it should be understood that various other changes and modifications may 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 appended claims cover all such changes and modifications that are within the scope of the claimed subject matter.
This application claims the benefit of U.S. Provisional Application No. 63/352,484 filed on Jun. 15, 2022, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63352484 | Jun 2022 | US |
