Production of 177Lu from Yb targets

Abstract

The present disclosure relates to a method for isolating lanthanides for diagnostic and / or therapeutic purposes, in particular for use in nuclear medicine, and to a method for isolating non-carrier-added (nca) lanthanides. 177 The present invention relates to a method for generating Lu.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This international patent application claims the benefit of U.S. Provisional Patent Application No. 63 / 292,286, filed December 21, 2021, which is incorporated by reference in its entirety.

[0002] Technical Field The present disclosure relates to a method for isolating lanthanides for diagnostic and / or therapeutic purposes, in particular for use in nuclear medicine, in particular non-carrier-added (nca) methods. 177 The present invention relates to a method for generating Lu. [Background technology]

[0003] Lutetium-177 (177 Lu) is available via the (n,γ) reaction. 177 There are two ways to generate Lu. One way is 176 Including irradiation with Lu, 177 This method, however, leads to the direct formation of the metastable 177m The presence of this long-lived isomer (half-life 160 days) results in the simultaneous formation of the 1,2-dichloro-1,2-triphenylphosphine isomer. 177 This significantly reduces the radionuclide purity of Lu. The long-lived isomers also pose serious problems for waste disposal.

[0004] The second method uses the short-lived radioisotope ytterbium-177 ( 177 Yb) (half-life 1.9 hours), which is concentrated 176 It is produced by neutron capture in a Yb (>99%) target. However, 176 Yb(n,γ)~ 177 The low thermal neutron cross section of the Yb reaction (2.85 barns) allows for a very small amount of the desired target compared to the total mass of the target. 177 In nuclear medicine, radioisotopes with high specific activity and high radionuclide purity are required, so the non-carrier-added (nca) with the highest specific activity is177 To obtain Lu, a trace amount 177 A significant amount of Lu 176 It must be separated from Yb (U.S. Pat. No. 6,716,353 B1).

[0005] Separation of the two lanthanides is difficult due to their similar chemical properties. Known separation methods include chromatographic methods such as ion exchange chromatography and extraction chromatography (U.S. Pat. No. 6,716,353 B1, G. Choppin, R. Silva, Journal of Inorganic and Nuclear Chemistry, 1956, vol. 3, no. 2, pp. 153-154). Due to the high mass ratio of Yb:Lu in the treated target after neutron capture, 177The separation of Lu requires excessive amounts of expensive chromatographic resins and involves a multi-step process, which makes the overall process time undesirably long, especially for commercial production (E. Horwitz, D. McAlister, A. Bond, R. Barans, J. Williamsons, A process for the separation of 177Lu from neutron irradiated 176Yb targets, Applied Radiation and Isotopes, 2005, vol. 63, no. 1, pp. 23-36; L. Van So, N. Morcos, M. Zaw, P. Pellegrini, I. Greguric et al., Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation. Part I. Multi-column chromatographic process for clinically applicable, Journal of Radioanalytical and Nuclear Chemistry, 2008, vol. 277, no. 3, pp. 663-673, 675-683). Furthermore, chromatographic methods achieve acceptable separation only at Yb:Lu mass ratios up to 1000:1 (R. Mikolajczak, “Separation of microgram quantities of Lu-177 from milligram amounts of Yb by the extraction chromatography”, 5 th (International Conference on Isotopes, Brussels, 2005). However, the mass ratio of Yb:Lu in the processed targets is typically significantly higher, by more than an order of magnitude.

[0006] An alternative method is Yb 3+ Yb 2+ by electrolytic reduction to and adsorption on a mercury electrode (amalgamation) 177Selective extraction of ytterbium from a Lu / Yb mixture Chemistry,2009,vol.280,no.1,pp.167-169,NALebedev,AFNovgorodov,R.Misiak,J.Brockmann,F.Rosch,Radiochemical separation of no-carrier-added 177Lu as produced via the 176Yb(n,γ)177Yb→177Lu process,Applied Radiation and Isotopes, 2000, vol. 53, no. 3, pp. 421-425). Recently, R. Chakravarty et al. reported a process involving two electrolysis steps that reportedly results in a 99% ytterbium isolation yield in the absence of a chromatographic purification step (R. Chakravarty, T. Das, A. Dash, M. Venkatesh, Radiochemical separation of no-carrier-added 177Lu as produced via the 176Yb177Yb 177Lu process, Nuclear Medicine and Biology, 2010, vol. 37, no. 7, pp. 811-820).However, an attempt to confirm the published separation yields revealed only an 82% separation yield after a two-stage electrolysis process that also involved amalgamation (I. Cieszykowska, M. Zoltowska, M. Mielcarski, Separation of ytterbium from 177Lu / Yb mixture by electrolytic reduction and amalgamation, SOP Transactions on Applied Chemistry 2014, vol. 1, no. 2, pp. 6-13). These authors achieved a separation yield of 94% by three-stage electrolysis, but this process did not produce nca with a very high level of purity. 177 It says it's not enough to get Lu.

[0007] Therefore, there remains a need for a time-efficient method that achieves very high separation of 177Lu from 176Yb and other impurities. For commercial production of 177Lu, a process is also needed that allows for processing several grams of treated target after neutron capture. There is also a need for a method for preparing nca177Lu with high specific activity.

[0008] Summary of the Invention The present disclosure relates to a method for separating product and non-product lanthanides in a mixture, comprising: separating the product and non-product lanthanides by electrolyzing the mixture; and controlling the pH of the mixture at about 6.0 to about 7.0 by adding a base during electrolysis of the mixture. The base may be an alkali metal hydroxide selected from the group consisting of lithium hydroxide, sodium hydroxide, and potassium hydroxide, preferably lithium hydroxide. By adding the base, the pH may be controlled at preferably about 6.5. The control of the pH may be periodic or continuous. Results to date suggest that controlling the pH at 6.5 using a base significantly improves the reduction of ytterbium (e.g., up to 99%) compared to using a lower pH. Furthermore, the inventors have been unable to reproduce published results showing high yields of ytterbium reduction by addition of hydrochloric acid during electrolysis.

[0009] The present disclosure also relates to a method for separating product and non-product lanthanides, comprising a step of preliminary electrolysis, in which an initial electrolyte solution comprising an alkali metal salt is conditioned by electrolysis such that at least a portion of the alkali metal ions of the alkali metal salt of the initial electrolyte solution are reduced to form mercury amalgam.

[0010] The alkali metal salt may be selected from alkali metal tartrates, alkali metal acetates, alkali metal citrates, and combinations thereof. The alkali metal may be lithium, sodium, or potassium. In one embodiment, lithium citrate is used. The step of conditioning the electrochemical cell reduces the oxidation state of at least a portion of the lithium ions and amalgamates the reduced lithium with the mercury cathode. Without being bound to a particular theory, the results thus far suggest that conditioning the initial electrolyte solution contributes substantially to the scale and effectiveness of the electrochemical separations disclosed herein.

[0011] The present disclosure also relates to a method for electrolytically separating product and non-product lanthanides in a mixture, comprising using a mercury cathode having a surface area that is "refreshed" during electrolysis to perform the electrolytic separation. More specifically, the surface area of ​​the mercury cathode is refreshed during electrolysis by stirring, flowing or circulating the mercury, and mercury at or near the interface with the separating electrolyte solution containing the lanthanide mixture is transported away from the interface after a relatively short period of time. This flow is intended to limit or even prevent the formation of a layer of reaction product(s) extending from the interface into the volume of the mercury cathode, which would tend to inhibit further reactions between mercury and the lanthanide mixture (e.g., reduction of the oxidation states of the non-product lanthanides and / or amalgamation of the reduced non-product lanthanides). The aforementioned flow of mercury may be accomplished using any suitable device configured for the electrolysis system, such as a pump (e.g., rotating lobe, rotating gear, piston, screw, diaphragm, etc.), impeller, propeller, and / or stir bar. In one embodiment, a stir bar is utilized due to the ease of integrating a stir bar into the electrolysis device.

[0012] Results to date suggest that the flow device must be selected, constructed, and operated to sufficiently move the mercury so as to limit or prevent the formation of an inhibitory reaction product layer without displacing the amalgamated solids from the bottom of the mercury cathode (or disturbing the amalgamated solids), as doing so would tend to alter the pH of the system. For example, rotating a PEEK-encapsulated cylindrical rare earth (NdBFe) magnet with dimensions of 3.56 cm in length and 1.14 cm in diameter (maximum energy product of 52 Megagauss Oersted (MGO)) at speeds ranging from 280 to 300 rpm has been shown to move the mercury through a 78.5 cm diameter magnet without stirring the amalgamated solids. 2 A mercury cathode having a surface area of ​​100 nm can be refreshed.

[0013] Selecting or controlling the surface area and the rate at which the surface area is refreshed can be used to affect the rate of electrochemical separation of ytterbium from lutetium. For example, the surface area of ​​the mercury cathode and electrolyte can be reduced to 44 cm while maintaining a flow of mercury. 2 From 78.5cm 2 (the volume of the electrolyte was kept the same, but the volume of the mercury was increased to 76 cm 3 From 101cm 3 to achieve an increase in the surface area inside the reaction vessel, a cylindrical round-bottom flask), from 0.045 to 0.12 min -1 The flow increased the separation rate as reflected by the first-order rate constant increasing with increasing flow rate. Flow was maintained using a 3.56 cm long × 1.14 cm diameter stir bar located on top of the mercury cathode and rotated at speeds ranging from 280 to 300 rpm. Although the platinum anode was modified, experiments varying the anode surface area and anode-cathode spacing showed that the difference in performance was due to the increased surface area of ​​the cathode-electrolyte interface. Also, the circulation rate of the electrolyte seemed to have little effect on the efficiency of the electrolytic separation. Furthermore, the volume of mercury was not a controlling factor, since more than the appropriate amount of Yb was amalgamated into a smaller volume of mercury. Stated differently, the increase in separation efficiency can be attributed almost entirely to the rate at which the surface area of ​​the mercury cathode was refreshed. The surface area of ​​the mercury cathode was approximately 40-120, 60-100, or 70-90, or 75-85 cm 2 The stirring speed may be selected from the ranges of 200 to 400, 250 to 350, 260 to 320, or 280 to 300 rpm.

[0014] The present disclosure also relates to a method for separating product and non-product lanthanides in a mixture, comprising dissolving the product and non-product lanthanides in the mixture with a solvent comprising trifluoromethanesulfonic acid and electrolyzing the mixture. In one embodiment, the solvent comprising trifluoromethanesulfonic acid has a concentration ranging from 3 M to 4 M. In another embodiment, the solvent comprising trifluoromethanesulfonic acid has a concentration ranging from 3.2 M to 3.6 M. The use of this acid avoids the disadvantages of using hydrochloric acid or other chloride sources, which tend to corrode platinum electrodes and oxidize mercury, thereby limiting the reuse of electrodes, particularly mercury cathodes.

[0015] In certain embodiments, the present disclosure provides a method for separating product lanthanides as well as non-product lanthanides in a mixture, comprising the steps of: (a) providing an electrochemical cell, the electrochemical cell comprising: a mercury cathode; Anode, and providing an initial electrolyte solution comprising alkali metal ions from an alkali metal salt dissolved in an initial solvent comprising water, the initial electrolyte solution being in contact with a mercury cathode and an anode; (b) adding a second solution to the initial electrolyte solution in the electrochemical cell to form a separate electrolyte solution in contact with the mercury cathode and the anode, the second solution comprising: a mixture comprising a product lanthanide and a non-product lanthanide; and forming a second solvent capable of dissolving said mixture including product lanthanides and non-product lanthanides without reacting with the anode and the mercury cathode; (c) separating the non-product lanthanide from the separated electrolyte solution, said separating being performed by operating the electrochemical cell to reducing the oxidation state of at least a portion of the non-product lanthanides and amalgamating the reduced non-product lanthanides with mercury at the mercury cathode without significant incorporation of the product lanthanides at the mercury cathode; and and recovering a product solution containing dissolved product lanthanides, thereby separating product lanthanides as well as non-product lanthanides.

[0016] In one particular embodiment, the method for separating product and non-product lanthanides may include a step of ion exchange using an anion exchange resin and aqueous hydrochloric acid solution, thereby separating at least a portion of the dissolved mercury ions.

[0017] In one particular embodiment, the method of separating the product and non-product lanthanides may comprise the step of chromatographic separation of the product lanthanides, the non-product lanthanides, and the alkali metal ions.

[0018] The present disclosure also provides a method for producing a product lanthanide, preferably a non-carrier added (nca) product lanthanide solution, more preferably a solution of nca177Lu, the method comprising: providing a mixture comprising a product lanthanide and a non-product lanthanide; - separating the product lanthanides and non-product lanthanides according to the separation methods described herein; - after the chromatographic separation step, concentrating the eluate containing the product lanthanide in an inert atmosphere, - product lanthanide, preferably a non-carrier-added (nca) product lanthanide solution, more preferably an nca 177 The present invention relates to a method for recovering a solution containing Lu. [Brief description of the drawings]

[0019] [Figure 1] 1 is a graph of the recovery rate of Yb as a function of time. [Diagram 2] 1 is a graph of the natural logarithm of Yb recovery as a function of time. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Electrolysis Steps The disclosed separation methods accomplish separation of product lanthanides from non-product lanthanides starting with a mixture comprising product lanthanides and non-product lanthanides. The disclosed method of separating product and non-product lanthanides includes a step of electrolysis utilizing an electrochemical cell. In certain embodiments, a method for separating product lanthanides as well as non-product lanthanides present in a mixture comprises: (a) providing an electrochemical cell, the electrochemical cell comprising: - mercury cathode, -Anode, and providing an initial electrolyte solution comprising alkali metal ions from an alkali metal salt dissolved in an initial solvent comprising water, the initial electrolyte solution being in contact with a mercury cathode and an anode; (b) adding a second solution to the initial electrolyte solution in the electrochemical cell to form a separated electrolyte solution in contact with the mercury cathode and the anode, the second solution comprising a mixture including product lanthanides and non-product lanthanides and a second solvent capable of dissolving the mixture including product lanthanides and non-product lanthanides without reacting with the anode and the mercury cathode; (c) separating the non-product lanthanides from the separated electrolyte solution, said separating comprising: - operating the electrochemical cell to reduce the oxidation state of at least a portion of the non-product lanthanides and amalgamate the reduced non-product lanthanides at the mercury cathode without significant incorporation of the product lanthanides at the mercury cathode; and - recovering a product solution comprising the dissolved product lanthanides; This separates the product lanthanides as well as the non-product lanthanides.

[0021] In one embodiment of the method, the product lanthanide is lutetium (Lu) and the non-product lanthanide is ytterbium (Yb). In one embodiment of the method, the product lanthanide is a radionuclide 177Lu, and the non-product lanthanide is 176 It is Yb.

[0022] In certain embodiments, the mixture containing product and non-product lanthanides can be of any origin. In one example, the mixture can be an irradiated target containing the mixture as an oxide. The irradiated oxide target can have a mass in the range of about 0.5 g to 10 g and a radioactivity in the range of about 555 GBq to about 15,000 GBq. The irradiated oxide target can be: 176 Yb, preferably enriched 176 The application of neutron irradiation to a Yb target and the target being heated to produce a short-lived radioisotope 177 It decays via beta decay of Yb (half-life 1.9 hours), 177 and enabling Lu to be generated. 176 The Yb target includes ytterbium oxide (Yb2O3).

[0023] Thus, in one embodiment, the mixture comprising the product lanthanides and the non-product lanthanides is 177 Lu and 176 The irradiation target may include a mixture of Yb and Yb. In one embodiment, the mixture is present as an oxide. 177 Lu and 176 Yb, i.e. 177 Lu2O3 and 176 It may include Yb2O3.

[0024] In certain embodiments, the mixture comprising the product lanthanide and the non-product lanthanide may have a mass ratio of non-product lanthanide to product lanthanide of about 1000:1 to about 4000:1. 177 Lu and non-product lanthanides 176 The mixture containing Yb is about 1000:1 to about 4000:1. 176 Yb vs. 177 Lu by mass ratio.

[0025] In step (a) of the method, an electrochemical cell is provided that includes a mercury cathode, an anode, and an initial electrolyte solution. The mercury cathode includes at least 99% mercury by weight. The mercury cathode may be about 99.999% mercury by weight. The mercury cathode may occupy the lower portion of the electrochemical cell. The mercury cathode may be agitated since it is a liquid. The mercury cathode may be agitated at the level of the upper surface of the mercury cathode. Alternatively, it may be agitated at the mid-height level of the mercury cathode during operation. The mercury cathode may be 78.5 cm 2 For a mercury cathode with a surface area of ​​about 40-120, 60-100, or 70-90, or 75-85 cm, it can be stirred with a stirring bar such as a PEEK encapsulated cylindrical rare earth (NdBFe) magnet (3.56 cm long × 1.14 cm diameter) with a maximum energy product of 52 Megagauss Oersted (MGO) at a speed ranging from 280 to 300 rpm. The surface area of ​​the mercury cathode can be about 40-120, 60-100, or 70-90, or 75-85 cm. 2 The stirring speed may be selected from the ranges of 200 to 400, 250 to 350, 260 to 320, or 280 to 300 rpm.

[0026] The anode comprises a metal (i.e., an anode metal) selected from the group consisting of ruthenium, rhodium, palladium, osmium, iridium, platinum, and alloys, mixtures, or combinations thereof. Preferably, the anode comprises platinum. In certain embodiments, the anode is about 10-40 cm 2 , preferably 25 to 35 cm 2 In certain embodiments, the anode may have a surface area in the range of about 10 to 40 cm. 2 , preferably 25 to 35 cm 2 The anode may comprise platinum having a surface area in the range of 0.1 to 1.0 mm. The anode is disposed in the initial electrolyte solution.

[0027] The initial electrolyte solution includes alkali metal ions derived from an alkali metal salt dissolved in an initial solvent including water, the initial electrolyte solution being in contact with a mercury cathode and an anode. The alkali metal ions may be selected from the group consisting of lithium ions, sodium ions, and potassium ions. Lithium ions may be preferred. In certain embodiments, the initial electrolyte solution may have an alkali metal ion concentration in the aqueous solvent ranging from about 0.15M to 0.90M, more preferably from about 0.30M to 0.75M, and most preferably from about 0.40M to 0.60M.

[0028] In certain embodiments, the alkali metal salt may be selected from the group consisting of alkali metal tartrates, alkali metal acetates, alkali metal citrates, and combinations thereof. Preferably, the alkali metal salt is lithium citrate.

[0029] In certain embodiments, the initial electrolyte solution may include lithium ions at a concentration of about 0.40-0.6M derived from lithium citrate dissolved in water, with the aqueous lithium citrate solution having a concentration of about 0.133M-0.25M.

[0030] The cathode and anode are connected to an externally provided power source and isolated from the electrochemical cell by wiring known to those skilled in the art, for example, ETFE coated wires may be selected for their resistance to degradation when exposed to chemicals used in electrolytic isolation and radiation.

[0031] In certain embodiments, step (b) of the method includes adding a second solution to the initial electrolyte solution in the electrochemical cell to form a separated electrolyte solution in contact with the mercury cathode and the anode. The second solution includes a mixture of product lanthanides and non-product lanthanides as described above, and a second solvent capable of dissolving the mixture including the product lanthanides and non-product lanthanides without reacting with the anode and the mercury cathode. In certain embodiments, the second solvent can be trifluoromethanesulfonic acid. In certain embodiments, the concentration of the second solvent used to dissolve the mixture can be 3-4M, preferably 3.2-3.6M, in the aqueous medium.

[0032] The advantage of using trifluoromethanesulfonic acid as the second solvent is that undesirable side reactions with the positive electrode or anode are suppressed or avoided, which contributes to increasing the yield of the electrolysis and amalgamation steps and reducing impurities. In particular, the acid avoids the erosion of the platinum anode and the oxidation of the mercury cathode, as observed with conventionally used hydrochloric acid or other chloride sources, allowing multiple reuse of the anode and mercury cathode.

[0033] In certain embodiments, step (b) of the method may further comprise dissolving the mixture comprising product and non-product lanthanides in a second solvent in a dissolution vessel, and the step of adding the second solution to the initial electrolyte solution comprises adding the contents of the dissolution vessel to the initial electrolyte solution.

[0034] In certain embodiments, step (b) may further comprise rinsing the dissolution vessel with a volume of a rinse solution, the rinse solution comprising the dissolved lithium salt described above, and the step of adding another solution to the initial electrolyte solution further comprises adding to the initial electrolyte solution the volume of the rinse solution used to rinse the dissolution vessel. The rinse solution may be a 1.0-1.5 M lithium citrate solution in water.

[0035] In step (c) of the method, the product lanthanide is separated from the separated electrolyte solution produced in step (b). Step (c) of separating the product lanthanide from the separated electrolyte solution comprises: - operating the electrochemical cell to reduce the oxidation state of at least a portion of the non-product lanthanides and amalgamate the reduced non-product lanthanides at the mercury cathode without significant incorporation of the product lanthanides at the mercury cathode; - recovering a product solution containing the dissolved product lanthanide, -Thereby separating product lanthanides from non-product lanthanides.

[0036] The electrochemical cell may be operated under an inert atmosphere with agitating / flowing / circulating the mercury cathode. Operating under an inert atmosphere may include passing an inert gas bubble through the separate electrolyte solution or purging the headspace of the electrochemical cell. Preferably, an inert gas may be bubbled through the separate electrolyte solution. The inert gas may be argon. The inert atmosphere has about atmospheric pressure.

[0037] Agitating the mercury cathode may include stirring at the level of the top surface of the mercury cathode or at the level of a mid-height of the mercury cathode.

[0038] In certain embodiments, reducing the oxidation state of at least a portion of the non-product lanthanide comprises reducing the oxidation state of an ytterbium(III) cation (Yb 3+ ) and amalgamating ytterbium metal with the cathode.

[0039] Typically, reducing the oxidation state of at least a portion of the non-product lanthanide is carried out by isotope-176 ytterbium(III) cation (Yb 3+ ) and amalgamating the isotope 176 ytterbium metal with the cathode.

[0040] In certain embodiments, reducing the oxidation state of at least a portion of the non-product lanthanides may include operating the electrochemical cell in a single continuous operation until at least 90% by weight, and preferably 99% by weight, of the non-product lanthanides are reduced and amalgamated at the cathode.

[0041] Step (c) comprises operating the electrochemical cell at a separation pH in the range of about 6.0 to about 7.0, preferably 6.5. In certain embodiments, step (c) comprises operating the electrochemical cell at a separation pH in the range of about 6.0 to about 7.0, a separation temperature in the range of about 10° C. to about 30° C., a separation potential in the range of about 5 V to about 10 V, and a separation current in the range of about 1 ampere to about 4 amperes, for a separation duration in the range of about 0.5 hours to about 4 hours.

[0042] For example, step (c) may include operating the electrochemical cell at a separation pH in the range of about 6.3 to about 6.7, a separation temperature in the range of about 15° C. to about 30° C., a separation potential in the range of about 7 V to about 9 V, and a separation current in the range of about 1.5 amps to about 3.5 amps, for a separation duration in the range of about 1.5 hours to about 2.5 hours.

[0043] In certain embodiments, step (c) may include operating the electrochemical cell at a separation temperature in the range of about 15° C. to about 30° C., a separation pH that is about 6.5, a separation duration of about 2 hours, and a separation potential of about 8 V and a separation current of about 2.5 amps.

[0044] The separation pH may be controlled during step (c) through periodic, continuous, or incremental addition of a base. The base may be an alkali metal hydroxide solution. The alkali metal hydroxide solution may be selected from the group consisting of lithium hydroxide, potassium hydroxide, and sodium hydroxide. The solution may have a concentration of about 3M. Preferably, a lithium hydroxide solution is used, which may have a concentration of about 3M.

[0045] Typically, step (c) of operating the electrochemical cell achieves less than 0.2% by weight of the product lanthanide being incorporated into the cathode.

[0046] In a particular embodiment, in step (c), the product solution comprising dissolved product lanthanides is recovered, thereby separating the product lanthanides and non-product lanthanides, and the product solution comprising the product lanthanides contains only trace amounts of mercury ions, preferably less than 20 ppm, more preferably less than 10 ppm, which is accomplished by a single continuous operation of one of the electrochemical cells.

[0047] Conditioning the electrochemical cell The disclosed method of separating product and non-product lanthanides may additionally include conditioning the electrochemical cell provided in step (a) prior to carrying out steps (b) and (c).

[0048] In certain embodiments, step (a) comprises conditioning an electrochemical cell as described above to: - reducing the oxidation state of at least a portion of the alkali metal ions contained in the initial electrolyte solution; -The reduced alkali metal is amalgamated with the mercury of the mercury cathode, The mercury cathode may additionally comprise an alkali metal amalgam.

[0049] Thus, in certain embodiments, the step of conditioning the electrochemical cell may include conditioning the electrochemical cell under an inert atmosphere, as described above under step (c). The inert atmosphere is typically applied for at least 30 minutes immediately prior to conditioning the cathode. The electrochemical cell may be agitated as described above.

[0050] The pH during conditioning can be as described above in step (c). In certain embodiments, the step of conditioning the electrochemical cell can include a conditioning pH in the range of about 6.0 to about 7.0, a conditioning temperature in the range of about 10° C. to about 30° C., a conditioning potential in the range of about 5 V to about 10 V, at a conditioning current in the range of about 1 ampere to about 4 amperes, and a conditioning duration in the range of about 0.5 hours to about 2 hours.

[0051] For example, the step of conditioning the electrochemical cell may include a conditioning pH in the range of about 6.3 to about 6.7, a conditioning temperature in the range of about 15° C. to about 25° C., a conditioning potential in the range of about 7 V to about 9 V, and a conditioning current in the range of about 1.5 amps to about 3.5 amps, for a conditioning duration in the range of about 0.5 hours to about 1.5 hours.

[0052] In certain embodiments, the step of conditioning the electrochemical cell may include a conditioning temperature in the range of about 15° C. to about 25° C., a conditioning pH that is about 6.5, a conditioning potential of about 8 V, and a conditioning current of about 2 amps for a conditioning duration of about 1 hour.

[0053] In certain embodiments, the adjusting step may include controlling the adjusted pH by adding a base. The base may be as described above in step (c). The base may be added periodically or continuously. Incremental addition of a lithium hydroxide solution, which may have a concentration of about 3M, is preferred.

[0054] For example, reducing the oxidation state of at least a portion of the alkali metal ions, preferably lithium ions, can include achieving a concentration of reduced alkali metal (preferably elemental lithium) relative to mercury, when measured immediately after conditioning, in the range of from about 50 ppm to about 1000 ppm, preferably from about 100 ppm to about 800 ppm, and most preferably from about 150 ppm to about 500 ppm.

[0055] The regulating step reduces the formation of impurities during electrolysis and provides a product solution with fewer impurities, thereby enabling the electrolysis of step (c) to be carried out on a significantly larger scale than prior art methods. The mode of operation of the electrochemical cell also has the advantage that the mercury can be reused multiple times without any adverse effect on the process or the resulting products.

[0056] In certain embodiments, the electrolysis of the present disclosure has the following characteristics: the product lanthanide being lutetium; the non-product lanthanide being ytterbium; the mercury cathode, prior to conditioning of the electrochemical cell, is about 99.999% mercury; the anode comprises a metal selected from the group consisting of ruthenium, rhodium, palladium, osmium, iridium, platinum, and alloys, mixtures, or combinations thereof; and the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.15M to about 0.90M; the alkali metal salt is selected from the group consisting of alkali metal tartrates, alkali metal acetates, alkali metal citrates, and combinations thereof; said conditioning including operating the electrochemical cell under an inert atmosphere with a controlled pH in the range of about 6.0 to about 7.0, a controlled temperature in the range of about 10° C. to about 30° C., a controlled potential in the range of about 5 V to about 10 V, and a controlled current in the range of about 1 ampere to about 4 amperes for a controlled duration in the range of about 0.5 hours to about 2 hours while agitating the cathode; the second solvent is trifluoromethanesulfonic acid; and Step (c) operating the electrochemical cell includes operating the electrochemical cell under an inert atmosphere with stirring the cathode at a separation pH in the range of about 6.0 to about 7.0, a separation temperature in the range of about 10° C. to about 30° C., a separation potential in the range of about 5 V to about 10 V, and a separation current in the range of about 1 ampere to about 4 amperes, for a separation duration in the range of about 0.5 hours to about 4 hours.

[0057] In another particular embodiment, the electrolysis of the present disclosure has the following characteristics: The product lanthanide is 177 Being Lu, The non-product lanthanide is 176 Being Yb, The mercury cathode, prior to conditioning of the electrochemical cell, is approximately 99.999% mercury; The anode includes platinum and is about 10 cm 2 ~about 40cm 2 having a surface area in the range of the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.30M to about 0.75M, the alkali metal salt is lithium citrate, the initial solvent is water, and the conditioning comprises operating the electrochemical cell under an inert atmosphere with agitation of the cathode at a controlled pH in the range of about 6.3 to about 6.7, a controlled temperature in the range of about 15°C to about 25°C, a controlled potential in the range of about 7V to about 9V, and a controlled current in the range of about 1.5 amps to about 3.5 amps for a controlled duration in the range of about 0.5 hours to about 1.5 hours; the second solvent is trifluoromethanesulfonic acid at a concentration ranging from about 2M to about 4M; and Step (c) operating the electrochemical cell includes operating the electrochemical cell under an inert atmosphere with stirring the cathode, at a separation pH in the range of about 6.3 to about 6.7, a separation temperature in the range of about 15° C. to about 25° C., a separation potential in the range of about 7 V to about 9 V, and a separation current in the range of about 1.5 amps to about 3.5 amps, for a separation duration in the range of about 1.5 hours to about 2.5 hours.

[0058] In another particular embodiment, the electrolysis of the present disclosure has the following characteristics: The product lanthanide is 177 Being Lu, The non-product lanthanide is 176 Being Yb, The mercury cathode, prior to conditioning of the electrochemical cell, is approximately 99.999% mercury; The anode is platinum and the anode is about 25 cm 2 ~Approx. 35cm 2 having a surface area in the range of the initial electrolyte solution has a lithium concentration in the range of 0.40M to about 0.60M, the lithium salt is lithium citrate, and the initial solvent is water; said conditioning including operating the electrochemical cell under an inert atmosphere with agitation of the cathode at a controlled temperature in the range of about 15° C. to about 25° C., a controlled pH of about 6.5, a controlled potential of about 8 V, and a controlled current of about 2 amps for a controlled duration of about 1 hour; the second solvent is trifluoromethanesulfonic acid at a concentration ranging from about 3 M to about 3.5 M; and Step (c) operating the electrochemical cell includes operating the electrochemical cell under an inert atmosphere with stirring the cathode, at a separation temperature in the range of about 15° C. to about 25° C., a separation pH that is about 6.5, for a separation duration of about 2 hours, and at a separation potential of about 8 V and a separation current of about 2.5 amps.

[0059] Ion exchange step In certain embodiments, the methods of the present disclosure may include a step of ion exchange to reduce the concentration of dissolved mercury ions in the solution containing the dissolved product lanthanide.

[0060] Typically, the method may include a step of ion exchange of a solution containing the product lanthanides using an anion exchange resin and aqueous hydrochloric acid, thereby reducing the dissolved mercury in the solution. The solution fed to this step may contain, in addition to the product lanthanides, alkali metal ions, traces of non-product lanthanides, and traces of dissolved mercury ions.

[0061] In a particular embodiment, the solution subjected to the ion exchange step may be the product solution containing the product lanthanide finally obtained in step (c). The ion exchange step is then typically carried out by: i. adding a volume of hydrochloric acid solution to the resulting solution to form an acidified solution; ii. passing the acidified solution through an ion exchange column containing an anion exchange resin such that the mercury ions are adsorbed onto the anion exchange resin to form a reduced mercury solution containing dissolved product lanthanide, non-product lanthanide, and alkali metal ions; iii. passing a rinse solution through the ion exchange column after passing the acidified solution to collect the product lanthanides, non-product lanthanides, and remaining amounts of lithium in the ion exchange column; The reduced mercury solution, the passed rinse, or a combination thereof is the ion exchange product solution.

[0062] For example, the hydrochloric acid solution can be approximately 11.5 M concentrated HCl in water. The anion exchange resin can be a styrene-divinylbenzene based resin. The rinse can be 0.15 M HCl in water.

[0063] The column had an internal diameter of 1 cm, a length of 10 cm, and was operated at ambient temperature at a rate of 3 mL / min, which was obtained by empirical optimization.

[0064] Although two or more steps of ion exchange may be performed in parallel or sequentially, the method according to the present disclosure should be based on one ion exchange column and perform only one single step of ion exchange to achieve sufficient mercury separation. Thus, in certain embodiments, the ion exchange step provides an ion exchanged product solution that may have a concentration of mercury that is 10 ppb or less.

[0065] Chromatographic separation steps In certain embodiments, the methods of the present disclosure may further comprise a step of chromatographic separation to reduce the concentrations of alkali metal ions, non-product lanthanides, and mercury ions.

[0066] In a preferred embodiment, the solution subjected to the chromatography step may be the ion-exchange product solution finally obtained in the ion-exchange step. As indicated above, the ion-exchange product solution may be the reduced mercury solution, the bled rinse, or a combination thereof. In one embodiment, the reduced mercury solution and the bled rinse are combined and the combination is subjected to chromatographic separation. In another embodiment, the reduced mercury solution and the bled rinse are subjected to sequential chromatographic separation (e.g., by placing ion-exchange and chromatography columns in series).

[0067] Typically, the chromatographic separation step comprises: i. loading the ion-exchanged product solution into a chromatography column containing a chromatography resin capable of adsorbing the product lanthanides and non-product lanthanides without adsorbing lithium ions, thereby adsorbing the product lanthanides and non-product lanthanides; ii. washing the packed chromatography column with a chromatography wash solution to remove alkali metal ions from the chromatography column without desorbing product and non-product lanthanides from the chromatography resin; iii. passing the chromatography elution solution through the washed chromatography column having adsorbed product and non-product lanthanides, wherein the product and non-product lanthanides desorb from the chromatography resin and separate as they move through the column in the chromatography elution solution at different rates according to the respective distribution coefficients of the column, thereby separating the product and non-product lanthanides into a product lanthanide-containing eluate and a non-product lanthanide-containing eluate, respectively.

[0068] The chromatography resin may comprise an alkyl derivative of phosphoric acid on an inert support, the alkyl derivative of phosphoric acid may be selected from the group consisting of di(2-ethylhexyl)orthophosphoric acid (HDEHP), 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (HEH[EHP]), and di-(2,4,4-trimethylpentyl)phosphinic acid (H[TMPeP]).

[0069] The chromatography resin may alternatively comprise an alkyl phosphate alkyl ester on an inert support. The chromatography resin may comprise (2-ethylhexyl)phosphonic acid-(2-ethylhexyl)-ester (HEH[EHP]) on an inert support.

[0070] The chromatographic wash solution can be 0.15 M aqueous HCl, the chromatographic eluent solution can be 1.4 to 1.5 M aqueous HCl, and the chromatographic column can be at a temperature ranging from about 40° C. to about 55° C., preferably from about 45° C. to about 50° C., during the chromatographic separation process.

[0071] The chromatographic separation step may be carried out after the ion exchange step, or alternatively, may be carried out first, such that the product solution finally obtained in step (c) of the present method may be loaded onto the chromatographic column of step i above and then ion exchange may be carried out. Preferably, the chromatographic separation is carried out after the ion exchange step.

[0072] Although two or more steps of chromatographic separation can be performed in parallel or sequentially, the method according to the present disclosure achieves excellent separation by performing only one single step of chromatographic separation based on one chromatographic column.

[0073] The chromatographic separation step additionally separates the mercury contained in the ion-exchange product solution to provide a product lanthanide-containing eluate having a mercury concentration that is less than 1 ppb.

[0074] Obtained 177 The Lu product has a specific activity of >2900 GBq / mg, high radiochemical purity (RCP) (>99%), and radionuclide purity (RNP) (>99.9%).

[0075] Reformulation Steps The methods of the present disclosure may further comprise the step of reformulating the solution obtained after chromatography / ion exchange.

[0076] The recombination step comprises recombining the product lanthanide-containing eluate finally obtained in the chromatographic separation step by heating the product lanthanide-containing eluate under an inert atmosphere to form a solid residue containing the product lanthanide.

[0077] In certain embodiments, the product lanthanide in the solid residue may be a product lanthanide chloride hydrate. Typically, the product lanthanide in the solid residue is 177 It can be LuCl3·nH2O. 177 LuCl3·nH2O has a specific activity ranging from about 2900 GBq / mg to about 4070 GBq / mg.

[0078] The solid residue can be redissolved (eg, using a 0.05 M HCl solution) to the desired activity concentration.

[0079] Step for recovery of non-product lanthanides The method of the present disclosure comprises: - contacting the mercury cathode and the electrochemical cell with an acidic solution to extract the non-product lanthanides therein to form a non-product lanthanide-containing solution; - precipitating the non-product lanthanide from the purified non-product lanthanide-containing solution with oxalic acid to form a non-product lanthanide oxalate; and - recovering the non-product lanthanide by pyrolyzing the non-product lanthanide oxalate salt to form recovered non-product lanthanide oxide.

[0080] In certain embodiments, the acidic solution may be selected from the group consisting of hydrochloric acid and trifluoromethanesulfonic acid.

[0081] In certain embodiments, the pyrolysis can be carried out at a temperature in the range of about 800°C to about 850°C.

[0082] In certain embodiments, the precipitated non-product lanthanide oxalate may be thoroughly washed to remove any lithium that may be present in the precipitate prior to thermally decomposing the salt in air.

[0083] In certain embodiments, the non-product lanthanide oxalate is 176 Yb2(O x )3 and the recovered non-product lanthanide oxide is 176 It is Yb2O3.

[0084] Method for producing a solution of a product lanthanide The present disclosure also provides a method for producing a lanthanide, preferably a nca 177 The present invention relates to a method for producing a solution of a non-carrier added (nca) product lanthanide solution, preferably Lu. The method comprises: - providing a mixture comprising product lanthanides and non-product lanthanides; and - separating the product lanthanides and non-product lanthanides according to the steps above, - after the chromatographic separation step, concentrating the eluate containing the product lanthanide in an inert atmosphere, - product lanthanide, preferably a non-carrier-added (nca) product lanthanide solution, more preferably an nca 177 The solution containing Lu is recovered.

[0085] The step of concentrating the eluate obtained after chromatographic separation may involve mild conditions such as evaporation by heating the solution under a flow of argon. The inert atmosphere may be provided by argon or nitrogen.

[0086] In certain embodiments, the solution recovered as the product of the process contains greater than 98% non-carrier added (nca) product lanthanides, preferably greater than 99% nca 177 In particular, the solution recovered as the product of the process may contain greater than 98% non-carrier-added (nca) product lanthanides, preferably greater than 99% nca with a specific activity of ≥ 2900 GBq / mg. 177 It may contain Lu.

[0087] In certain embodiments, the method of producing can include providing about 0.5-10 g and about 555 GBq-15,000 GBq of a mixture of product and non-product lanthanides. The mixture of product and non-product lanthanides can be irradiated with neutrons. 176 Yb, preferably ytterbium oxide, is applied to a target to produce a radioisotope 177 Yb is produced and the target decays after beta decay. 177 From Yb 177 Lu can be generated by enabling generation of EXAMPLES

[0088] The objectives of the chemical process are (a) to separate trace (mg) levels of Lu from bulk (gram) levels of Yb, and (b) to recover a high yield of Yb from the process. Separation is accomplished by reducing Yb to a mercury cathode and then using chromatography to separate the trace amounts of Yb in the electrolyte solution from the Lu. The Yb target material is recovered from the mercury cathode by extraction with triflic acid, followed by precipitation with oxalic acid and ashing of the oxalate compound to Yb oxide.

[0089] The electrochemical cell (EC) consisted of a mercury cathode, a platinum anode, and a 0.16 M lithium citrate electrolyte. After thorough purging with argon to remove oxygen, the EC cell was operated at 8.0 V for 30 minutes and the pH was controlled at 6.5 by LiOH addition to create lithium mercury amalgam. A Yb2O3 target was dissolved in triflic acid and then added to the EC cell, and electrolysis was continued until the Yb concentration was reduced by at least 99% by reductive amalgamation. During electrolysis, the EC cell was maintained at a temperature of 20 degrees Celsius, the surface of the cathode was continuously stirred, the pH of the solution was maintained at 6.5 by continuous addition of LiOH, and the EC was continuously purged with argon gas.

[0090] Once the desired Yb separation is achieved, the electrolyte solution is removed from the EC. The electrolyte solution is filtered and acidified by the addition of HCl acid. The electrolyte solution is then passed through an anion exchange resin pre-equilibrated with HCl to remove traces of mercury from the solution.

[0091] The solution from the anion exchange resin is then loaded onto a LN2 resin and the traces of Yb in the solution are separated from the Lu in the solution by eluting with 1.4 M HCl. The LN2 column is maintained at a temperature of 50° C. for the separation process. Yb is eluted from the column first, and then Lu is eluted and collected.

[0092] The Lu eluate is dried and reconstituted in 0.05M HCl to produce the desired activity concentration in the product. The enriched Yb target material is recovered from the mercury cathode by washing with triflic acid. The Yb in the triflic acid recovery solution is precipitated by the addition of oxalic acid. The ytterbium oxalate is converted back to ytterbium oxide target material by ashing (or pyrolysis) the precipitate to 850 °C.

[0093] Equipment, materials, and detailed steps: An electrochemical cell was provided with a volume of 1000 mL and a diameter of 10 cm. The electrochemical cell had a round bottom and was water jacketed. It held approximately 1360 g of mercury (cathode) and a NdBFe magnet. It was equipped with a PEEK lid with fitting Pt (platinum) electrodes (anode and cathode contacts), a pH recirculation reservoir and tubing, an argon bubbler, a LiOH (lithium hydroxide) dispense line, and a vent / access hole.

[0094] A Dowex 1x8 (Cl-) column (1 cm diameter, 10 cm length) equilibrated in 0.15 M HCl was used for ion exchange.

[0095] A water-jacketed LN2 column (1.1 cm diameter, 40 cm length) equilibrated in 0.15 M HCl was used for the chromatographic separation. The LN2 column contains (2-ethylhexyl)phosphonic acid-(2-ethylhexyl)-ester (HEH[EHP]) on an inert support as the stationary phase.

[0096] 1. Target dissolution: a. The irradiated Yb2O3 target was transferred from the quartz target vial to a target dissolution vial. b. 3.4 M triflic acid (trifluoromethanesulfonic acid) was added to the dissolution vial. The target sample solution was heated at approximately 100° C. under continuous stirring until the target material was completely dissolved. c. Once dissolved, the target solution was cooled to room temperature.

[0097] 2. Electrochemical Cell Preparation a. The thermostatic recirculator was set to 20° C. and the flow to the jacketed electrochemical cell was started. b. 187 grams of 0.16 M lithium citrate electrolyte solution was added to the electrochemical cell. c. A slow argon purge of the electrochemical cell was started and stirring of the surface of the mercury cathode was commenced. d. The peristaltic pump was turned on to slowly recirculate the electrolyte through the pH loop. The flow rate was adjusted so that the returning electrolyte steadily dripped into the electrochemical cell, but did not form a continuous stream. e. During electrolysis, the pH was maintained at 6.5 by continuous addition of 3.0 M LiOH. f. The electrolyte solution was purged with argon continuously throughout the electrochemical process, at least 30 minutes prior to the start of electrolysis.

[0098] 3. Electrolysis a. After argon purging for at least 30 min, preliminary electrolysis was started at a potential of 8.0-8.1 V. b. During pre-electrolysis, the argon purge was continued and the pH was maintained at 6.5 by incremental addition of 3.0 M LiOH. c. Pre-electrolysis was continued for approximately 30 minutes. d. After 30 min of pre-electrolysis, the target solution was added without stopping the electrolysis. e. Electrolysis was continued until >99% Yb reduction in the electrolyte solution was achieved. The pH was maintained at 6.5 during electrolysis by addition of LiOH. f. Upon completion of electrolysis, the following steps were carried out quickly: 1. Stop adding LiOH. 2. Raise the pH loop sipper tubing above the liquid level in the electrochemical cell and pump until the line clears. 3. Raise the argon purge line above the liquid level. 4. Turn off the magnetic stirrer. 5. Rapidly vacuum transfer the electrolyte from the electrochemical cell to the receiver bottle, being careful not to aspirate the mercury with the solution. g. The electrolyte was then filtered through a 0.2 micron PES membrane into a 250 mL Nalgene bottle. h. 7.0 mL of concentrated HCl was added to the filtered electrolyte.

[0099] 4. Chromatographic Purification a. Water recirculation through the LN2 column jacket was set at 50° C. to heat the column before electrolyte input into the Dowex-LN2 column series. The output of the Dowex ion exchange column is connected in series to the input of the LN2 column. b. The pH-adjusted electrolyte solution was packed into a Dowex 1x8 column and passed through a LN2 column at a flow rate of 2-3 mL / min. c. The chromatography system was rinsed with 70 mL of 0.15 M HCl at a flow rate of 2-3 mL / min. d. The LN2 column was rinsed with 150 mL of 0.15 M HCl at a flow rate of 2-3 mL / min. e. Traces of Yb and Lu products were eluted from the LN2 column using 1.4 M HCl. Yb elutes in about the first 200 mL, followed by dissolution of Lu, thereby yielding a product solution containing dissolved lutetium.

[0100] 5. Yb recovery after electrolysis a. 200 mL of 1.0 M triflic acid was added to the electrochemical cell and gently stirred to clean the anode electrode. b. The anode electrode was raised to the top of the EC cell and then the acid extractant was vigorously stirred for about 30 minutes. c. A vacuum transfer of the triflic acid recovery solution was performed from the EC cell to a 500 mL Nalgene bottle, which contained the Yb target material. d. 100 mL of 0.05 M triflic acid rinse solution was added to the electrochemical cell and stirred vigorously for approximately 10 minutes. e. A vacuum transfer of the triflic acid rinse solution to the triflic acid recovery solution was performed. f. The combined triflic acid recovery / rinse solution was filtered through a 0.2 μm PES filter into a Nalgene filter bottle.

[0101] 6.Yb target recycling a. After sufficient collapse, Yb from the triflic acid recovery / rinse solution was precipitated by adding a 50% molar excess of oxalic acid to the solution. b. The precipitate suspension was filtered through ashless filter paper and the precipitate was then washed with water. c. The precipitate and filter paper were placed in a quartz vial and heated to approximately 850°C to decompose the filter paper and convert the Yb2(C2O4)3 to Yb2O3.

[0102] As shown in the figure below, the electrochemical separation of Yb from the electrolyte solution follows a first-order kinetic law. Many of the electrochemical separation process parameters are optimized to achieve maximum speed of the separation process in order to minimize the time of electrochemical separation. Minimizing the separation time increases the overall Lu yield from the process (by reducing losses due to radioactive decay) and minimizes the effect of radiolysis on the efficiency of the separation process. The rate constant k of the separation process is determined from the slope of the natural logarithm of the Yb concentration in the electrolyte solution versus time. For example, 99% separation occurs within 0.10 min -1 This is achieved in 46 minutes for a process with a rate constant of 0.05 minutes. -1 This is achieved in 92 minutes with a rate constant of .

[0103] 1. Baseline Initial development work for the process began when we constructed a prototype EC cell: a 450 mL Ace jacketed beaker (7.48 cm ID (43.9 cm)) for temperature control, equipped with fabricated closures with compression fittings for electrodes, pH recirculation loop, LiOH dosing, and argon purging. 2 The researchers used what they called the surface area of ​​mercury (Hg surface area). After numerous small scale tests to rough out the process, 2.5g Yb as Yb2O3 / HOTf became the usual scale for optimization in prototype cells. For all processes, tracers 175 Yb (approximately 370 MBq) was used to monitor the reaction progress by high purity gamma spectroscopy. Tracer Lu-177 was also used to confirm complete recovery in the process, if necessary. A constant potential of 8.0 V DC was found to be optimal for best Yb separation in the prototype system. Anode and cathode contact electrodes were fabricated using readily available Pt wire: Pt wire loop anode (1 mm diameter x approx. 50 cm), approx. 908 g Hg cathode (1 mm diameter x approx. 25 cm) with Pt wire loop contact (anode / cathode spacing was maintained at approx. 1.5 cm) Initial testing optimized the process chemistry as follows: 187 mL 0.16 M lithium citrate electrolyte, 1 hour pre-electrolysis and approximately 2 hours of Yb electrolysis to achieve >99Yb depletion in the electrolyte, pH was controlled at 6.5 with 3.0 M LiOH throughout the process. Prior to and continuously throughout the process, the electrochemical cell was purged with high purity argon. A cold water recirculation system was used to maintain the temperature at 20°C during the process. Following target addition after pre-electrolysis, 10.0 g of 1.33 M LiCit was added to achieve the optimal citrate / Yb ratio, and 6.75 g of 3.0 M LiOH was added to neutralize the excess trifluoromethanesulfonic acid required to dissolve the Yb2O3 target. First order rate constant (derived from a plot of ln(Yb-175) vs. time) k = 0.0462 min -1 (average of 11 runs) - corresponds to about 99% Yb reduction in 100 min.

[0104] 2. Process Capability · Prototype EC, baseline system as above with increased target (5.0 g Yb) and tracer Yb-175. - Rate constant k = 0.0324 min, which corresponds to 99% Yb reduction in about 142 min -1 - The first 5.0g trial was successful in reducing Yb but suffered complications from mercury by-products. · Baseline system containing prototype EC, 25% extra LiCit, 25% extra Hg, and 5.0g Yb with Yb-175 tracer. ·Rate constant k=0.0333min -1 Essentially the same Yb reduction, but with significantly less mercury by-product.

[0105] 3. Preliminary Electrolysis First high activity process (15Ci Lu-177 and 0.5g Yb) using a prototype EC baseline system The required 99% Yb reduction could not be achieved. A maximum of -ΔYb of only 89.4% was reached. Hypothesis: Interference from radiolysis products such as hydrogen peroxide. High activity (15Ci Lu-177 and approximately 0.5g Yb) was reproduced in a prototype EC baseline system modified by (1) incorporation of a 1-h pre-electrolysis step prior to target introduction, (2) addition of an additional lithium citrate post-target, and (3) installation of a Pt mesh to catalyze hydrogen peroxide decomposition. Achieved 99% Yb separation in 2 hours in three separate experiments, with a first-order rate constant k ≈ 0.055 min -1 Hypothesis: (1) Lithium amalgam plays an important role in the reduction and amalgamation of Yb, so preloading the amalgam before target addition accelerates the Yb reaction significantly. This is supported by the observation of a higher rate constant during the initiation of Yb electrolysis. (2) Additional lithium citrate added immediately after target addition helps the formation of citrate-Yb complexes that favor Yb electrolysis. (3) The added Pt mesh could potentially help minimize interference from radiolysis products. We believe that the preloading of lithium amalgam is the main reason for the success of the process. This observation has not been reported in the literature.

[0106] 4. Higher concentrations of radiolytic products Due to obvious radiolysis issues in the 15Ci Lu-177, 0.5g Yb test, scaling up to higher activity (70Ci Lu-177, 2.35g Yb) was an important step towards a full commercial process. A small-scale prototype EC cell baseline system used for preliminary electrolytic filling of lithium amalgam 99% Yb separation was achieved by extending the electrolysis to 4 hours. The obtained rate constant (k = 0.0162 min -1) was significantly lower than for the previous 15Ci Lu-177 process, confirming concerns about high activity targets. Reminder: no such reduction in rate constants was observed in low activity tracer studies over a wide range of target sizes.

[0107] 5. Optimizing process pH Using a small-scale prototype baseline system, experiments were carried out to determine the optimal pH for Yb electrolysis. At controlled low pH, the efficiency of Yb reduction amalgamation decreased, e.g., at pH 6.0, the maximum Yb depletion in the electrolyte was 95%. At higher pH (e.g. pH 7.0), interference from mercury compounds compromised the process.

[0108] 6. Optimization of lithium citrate concentration A small-scale prototype baseline system was used to vary the lithium citrate concentration from 0.16M to 0.32M. The rate constant was best at a lithium citrate concentration of 0.16M. [LiCit]=0.16M k=0.0482min -1 , [LiCit]=0.24M k=0.0249min -1 , [LiCit]=0.32M k=0.0189min -1

[0109] 7. Electrochemical Cell Potential Optimization A small-scale prototype baseline system was used to vary the cell potential from 7.0V to 9.0V. The rate constant showed that a potential of 8.0 V was ideal. 7.0 V k=0.0236 min -1 , 8.0V k=0.0482min -1 , 9.0V k=0.0317min -1 In addition to process efficiency, i.e., rate constants, potentials above 8.0 V posed problems with mercury by-products.

[0110] 8. Beta Baseline The limitations of the small-scale prototype electrochemical cell led to the search for a version suitable for routine production and to improve the process efficiency, i.e., a larger Yb depletion rate constant. The search results show that the Beta EC cell has a larger volume and a larger mercury cathode surface area (78.5 cm 2 The flask was fitted with a 1000 mL Ace jacketed round bottom flask with a 10.0 cm ID. -Multiple tracer tests (370MBq) to improve processes and associated equipment 175 With Yb, 2.5 g of Yb was carried out as Yb2O3 / HOTf. Beta EC Cell Parameters: o Electrodes: 6 mm wide Pt ribbon anode (diameter approximately 7.6 cm), approximately 1300 g Hg cathode with Pt wire contacts approximately 5 cm long (anode / cathode spacing approximately 1.25 cm) Cathode surface stirred at 270 rpm with oPEEK encapsulated RE magnet Process parameters: o 187mL 0.16M LiCit, pre-electrolysis for 30 minutes, pH controlled at 6.5 with 3.0M LiOH o Pretreatment and continuous argon purge, temperature was maintained at 20°C. Following the addition of the oYb target, add 10.0g 1.33M LiCit to maintain the proper citrate / Yb ratio, and 6.75g 3.0M LiOH to neutralize excess acid and adjust the system to the proper pH. The rate constant was significantly improved compared to the prototype system experiments, k=0.124±0.005min -1 (n=6) · Hypothesis: The significant increase in the rate constant is primarily a result of the larger surface area of ​​the mercury cathode in the beta version of the E-cell.

[0111] 9. Acid used to recover Yb from mercury cathodes In a baseline study with a beta EC cell, the Yb target material was recovered from the mercury cathode at the end of the process by extraction with 2.25M HCl. Beta baseline, Yb recovery using 2.25MHCl, recycled mercury As with the small-scale prototype testing, the mercury was collected after each process, rinsed with water and then cleaned before being recycled for subsequent testing. In the baseline beta test, the recycled mercury was visibly degraded by the accumulation of mercuric chloride and mercury platinum compounds over four consecutive runs, as evidenced by its deteriorated appearance and reflected in the rate constants of the four consecutive processes. Run 1 k=0.104min -1 , execution time 2 k=0.131min -1 , execution 3 k=0.083min -1 , execution 4 k=0.066min -1 It was hypothesized that hydrochloric acid causes these deleterious effects due to the formation of chlorine which reacts with the mercury and platinum anodes to form oxidation products. Subsequent substitution of trifluoromethanesulfonic acid for Yb target recovery was evaluated and found to eliminate contamination of recycled mercury and decomposition of the platinum anode. It was also discovered through extensive testing that the acid concentration could be reduced to 1.0M. In 12 continuous tracer tests using a 2.5 g Yb target, no visible decomposition of mercury was observed, and the rate constant was highly reproducible: k = 0.125 ± 0.006 min -1 (n=12)

[0112] 10. Stirring speed on the surface of the mercury cathode The renewal of the mercury cathode surface by controlled stirring was found to be a key parameter for the process efficiency in the beta EC cell. As an example, when the stirring speed was decreased from 270 to 190 rpm, the Yb depletion rate constant k = 0.125 min -1 From k=0.058min -1 was reduced to Note that the stirring must occur at the surface of the mercury. If the stirring speed is too high, the stir bar will dip into the mercury and thus may disturb the amalgam formed below the surface.

[0113] Embodiment 1. A method for separating product lanthanides and non-product lanthanides in a mixture, the method comprising: a. providing an electrochemical cell, the electrochemical cell comprising: i. mercury cathode, ii. an anode; and iii. providing an initial electrolyte solution comprising alkali metal ions from an alkali metal salt dissolved in an initial solvent comprising water, the initial electrolyte solution being in contact with a mercury cathode and an anode; b. adding a separate solution to the initial electrolyte solution in the electrochemical cell to form a separate electrolyte solution in contact with the mercury cathode and the anode, the separate solution being i. a mixture comprising a product lanthanide and a non-product lanthanide; and ii. forming a second solvent capable of dissolving the mixture including product lanthanides and non-product lanthanides without reacting with the anode and the mercury cathode; c. separating the non-product lanthanide from the separated electrolyte solution, said separating being performed by operating the electrochemical cell to i. reducing the oxidation state of at least a portion of the non-product lanthanides; ii. amalgamating the reduced non-product lanthanide with mercury at a mercury cathode; and iii. recovering a product solution containing the dissolved product lanthanide; This separates the product lanthanides as well as the non-product lanthanides.

[0114] 2. The method of embodiment 1, wherein the step (a) of providing an electrochemical cell comprises conditioning the electrochemical cell to reduce the oxidation state of at least a portion of the alkali metal ions and cause the reduced alkali metal to amalgamate with the mercury of the mercury cathode such that the mercury cathode additionally comprises an alkali metal amalgam.

[0115] 3. The method of embodiment 1 or 2, wherein the product lanthanide is lutetium and the non-product lanthanide is ytterbium.

[0116] 4. The product lanthanide is 177 Lu and the non-product lanthanide is 176 The method according to any one of embodiments 1 to 3, wherein Yb is

[0117] 5. The method of any one of the preceding embodiments, wherein the mercury cathode is about 99.999% mercury prior to conditioning the electrochemical cell according to step (b) of embodiment 2 or embodiment 1.

[0118] 6. The method of any one of the preceding embodiments, wherein the anode comprises a metal selected from the group consisting of ruthenium, rhodium, palladium, osmium, iridium, platinum, and alloys, mixtures, or combinations thereof.

[0119] 7. The method of embodiment 6, wherein the anode comprises platinum.

[0120] 8. The anode is about 10 cm 2 ~about 40cm 2 Preferably, about 25 cm 2 ~about 35cm 2 8. The method of claim 6 or 7, having a surface area in the range of

[0121] 9. The cathode is 40 cm 2 ~120cm 2 , preferably 60cm 2 ~100cm 2 , more preferably 70 cm 2 ~90cm 2, most preferably 75 cm 2 ~85cm 2 9. The method according to any one of the preceding claims, having a surface area of

[0122] 10. The method according to any one of the preceding embodiments 1 to 9, wherein the cathode is stirred at a speed of 200 to 400 rpm, preferably 250 to 350 rpm, more preferably 260 to 320 rpm, and most preferably 280 to 300 rpm.

[0123] 11. The method of any one of the preceding embodiments 1 to 10, wherein the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.15M to about 0.90M, more preferably 0.30M to 0.75M, and most preferably 0.40M to 0.60M.

[0124] 12. The method according to any one of the preceding embodiments, wherein the alkali metal ions are selected from the group consisting of lithium ions, sodium ions, and potassium ions, preferably lithium ions.

[0125] 13. The method of any one of the preceding embodiments, wherein the alkali metal ion is derived from an alkali metal salt selected from the group consisting of alkali metal tartrates, alkali metal acetates, alkali metal citrates, and combinations thereof.

[0126] 14. The method of any one of the preceding embodiments, wherein the alkali metal salt is lithium citrate.

[0127] 15. The method of any one of embodiments 2 to 14, wherein step (a) comprises conditioning the electrochemical cell under an inert atmosphere.

[0128] 16. The method of any one of embodiments 2 to 15, wherein step (a) comprises conditioning the electrochemical cell with an adjusted pH in the range of about 6.0 to about 7.0, an adjusted temperature in the range of about 10°C to about 30°C, an adjusted potential in the range of about 5V to about 10V, and an adjusted current in the range of about 1 ampere to about 4 amperes, for an adjusted duration in the range of about 0.5 hours to about 2 hours, while agitating the cathode.

[0129] 17. The method of any one of the preceding embodiments, wherein the second solvent is trifluoromethanesulfonic acid.

[0130] 18. The method of embodiment 17, wherein the concentration of the second solvent is 2M to 4M, preferably 3 to 3.5M.

[0131] 19. The method of any one of the preceding embodiments, wherein step (c) comprises operating the electrochemical cell under an inert atmosphere while stirring the cathode.

[0132] 20. The method of any one of the preceding embodiments, wherein step (c) comprises operating the electrochemical cell at a separation pH in the range of 6.0 to 7.0, preferably 6.5.

[0133] 21. The method of any one of embodiments 1 to 21, wherein step (c) comprises operating the electrochemical cell at a separation pH in the range of about 6.0 to about 7.0, a separation temperature in the range of about 10°C to about 30°C, a separation potential in the range of about 5V to about 10V, and a separation current in the range of about 1 ampere to about 4 amperes, for a separation duration in the range of about 0.5 hours to about 4 hours.

[0134] twenty two. the product lanthanide is lutetium; the non-product lanthanide is ytterbium; The mercury cathode before conditioning the electrochemical cell is approximately 99.999% mercury; the anode comprises a metal selected from the group consisting of ruthenium, rhodium, palladium, osmium, iridium, platinum, and alloys, mixtures, or combinations thereof; the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.15M to about 0.90M, and the alkali metal salt is selected from the group consisting of an alkali metal tartrate, an alkali metal acetate, an alkali metal citrate, and combinations thereof; the conditioning includes operating the electrochemical cell under an inert atmosphere with a controlled pH in the range of about 6.0 to about 7.0, a controlled temperature in the range of about 10° C. to about 30° C., a controlled potential in the range of about 5 V to about 10 V, and a controlled current in the range of about 1 ampere to about 4 amperes for a controlled duration in the range of about 0.5 hours to about 2 hours while agitating the cathode; the second solvent is trifluoromethanesulfonic acid; 2. The method of embodiment 1, wherein step (c) comprises operating the electrochemical cell at a separation pH in the range of about 6.0 to about 7.0, a separation temperature in the range of about 10° C. to about 30° C., a separation potential in the range of about 5 V to about 10 V, and a separation current in the range of about 1 ampere to about 4 amperes, with stirring at the cathode, for a separation duration in the range of about 0.5 hours to about 4 hours.

[0135] twenty three. The product lanthanide is 177 Lu, The non-product lanthanide is 176 Yb, The mercury cathode before conditioning the electrochemical cell is approximately 99.999% mercury; The anode includes platinum and is about 10 cm 2 ~about 40cm 2 and having a surface area in the range of the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.30 M to about 0.75 M, the alkali metal salt is lithium citrate, and the initial solvent is water; the conditioning includes operating the electrochemical cell under an inert atmosphere with agitation of the cathode at a controlled pH in the range of about 6.3 to about 6.7, a controlled temperature in the range of about 15° C. to about 25° C., a controlled potential in the range of about 7 V to about 9 V, and a controlled current in the range of about 1.5 amps to about 3.5 amps for a controlled duration in the range of about 0.5 hours to about 1.5 hours; and the second solvent is trifluoromethanesulfonic acid at a concentration in the range of about 2 M to about 4 M; 2. The method of embodiment 1, wherein step (c) comprises operating the electrochemical cell under an inert atmosphere with a separation pH in the range of about 6.3 to about 6.7, a separation temperature in the range of about 15° C. to about 25° C., a separation potential in the range of about 7 V to about 9 V, and a separation current in the range of about 1.5 amps to about 3.5 amps for a separation duration in the range of about 1.5 hours to about 2.5 hours while agitating the cathode.

[0136] twenty four. The product lanthanide is 177 Lu, The non-product lanthanide is 176 Yb, The mercury cathode before conditioning the electrochemical cell is approximately 99.999% mercury; The anode is platinum and the anode is about 25 cm 2 ~about 35cm 2 and having a surface area in the range of the initial electrolyte solution has lithium citrate as the alkali metal salt with a lithium ion concentration in the range of 0.40M to about 0.60M, and the initial solvent is water; the conditioning includes operating the electrochemical cell under an inert atmosphere with a conditioning temperature ranging from about 15° C. to about 25° C., a conditioning pH of about 6.5, a conditioning potential of about 8 V, and a conditioning current of about 2 amps for a conditioning duration of about 1 hour while stirring the cathode; the second solvent is trifluoromethanesulfonic acid at a concentration ranging from about 3 M to about 3.5 M; 2. The method of embodiment 1, wherein step (c) comprises operating the electrochemical cell under an inert atmosphere with stirring the cathode at a separation temperature ranging from about 15° C. to about 25° C., a separation pH that is about 6.5, a separation duration of about 2 hours, and a separation potential of about 8 V and a separation current of about 2.5 amps.

[0137] 25. The method according to any one of embodiments 15 to 24, wherein the adjusting pH during the adjusting step (a), or the separating pH during the separating step (c), or the adjusting pH and the separating pH are controlled by the addition of a base.

[0138] 26. The method of embodiment 25, wherein the base is an alkali metal hydroxide.

[0139] 27. The method of embodiment 26, wherein the base is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, preferably lithium hydroxide.

[0140] 28. The method of any one of embodiments 25-27, wherein controlling the separation pH is cyclic or continuous.

[0141] 29. The method of any one of embodiments 25-28, wherein controlling the separation pH is by incremental addition of lithium hydroxide solution.

[0142] 30. The method of embodiment 29, wherein the lithium hydroxide solution has a concentration of about 3M.

[0143] 31. The method of any one of embodiments 15-30, wherein the inert atmosphere is an argon purge at about atmospheric pressure.

[0144] 32. The method of any one of embodiments 15-31, wherein an argon purge is performed for at least 30 minutes immediately prior to conditioning the cathode.

[0145] 33. The method of any one of embodiments 2 to 32, wherein immediately after the conditioning step, the cathode comprises a reduced alkali metal, preferably lithium, in a concentration ranging from about 50 ppm to about 1,000 ppm relative to mercury.

[0146] 34. The method of any one of embodiments 2 to 32, wherein immediately after the conditioning step, the cathode comprises a reduced alkali metal, preferably lithium, in a concentration ranging from about 100 ppm to about 800 ppm relative to mercury.

[0147] 35. The method of any one of embodiments 2 to 32, wherein immediately after the conditioning step, the cathode comprises a reduced alkali metal, preferably lithium, in a concentration ranging from about 150 ppm to about 500 ppm relative to mercury.

[0148] 36. The method of any one of embodiments 1 to 35, wherein the mixture containing product lanthanides and non-product lanthanides is from an irradiated target containing the mixture as oxides, preferably the irradiated target having a mass in the range of about 0.5 g to about 10 g and a radioactivity in the range of about 555 Gbq to about 15,000 Gbq.

[0149] 37. The method of embodiment 36, further comprising dissolving the mixture comprising product lanthanides and non-product lanthanides in a second solvent in a dissolution vessel, and the step of adding another solution to the initial electrolyte solution comprises adding the contents of the dissolution vessel to the initial electrolyte solution.

[0150] 38. The method of claim 1, further comprising rinsing the dissolution vessel with a volume of a rinse solution, the rinse solution comprising a dissolved lithium salt selected from the group consisting of lithium tartrate, lithium acetate, lithium citrate, and combinations; 38. The method of embodiment 37, wherein the step of adding another solution to the initial electrolyte solution further comprises adding to the initial electrolyte solution the volume of rinsing solution used to rinse the dissolution vessel.

[0151] 39. The method of embodiment 38, wherein the rinsing solution is a 1.0 to 1.5 M aqueous solution of lithium citrate.

[0152] 40. The method of any one of the preceding embodiments, wherein the other solution has a mass ratio of non-product lanthanide to product lanthanide in the range of about 1000:1 to about 4000:1.

[0153] 41. The method of any one of the preceding embodiments, wherein the separating step (c) is a single continuous operation of the electrochemical cell until at least 90% of the non-product lanthanide in the separating electrolyte solution has been reduced and amalgamated with the mercury cathode.

[0154] 42. The method of any one of the preceding embodiments, wherein the separating step (c) is a single continuous operation of the electrochemical cell until at least 99% of the non-product lanthanide in the separating electrolyte solution is reduced and amalgamated with the mercury cathode.

[0155] 43. The method of embodiment 42, wherein the product solution containing dissolved product lanthanides contains 20 ppm or less of mercury.

[0156] 44. The method of any one of the preceding embodiments, comprising the step of performing ion exchange of the product solution containing dissolved product lanthanides using an anion exchange resin, thereby reducing dissolved mercury in the product solution, and recovering the ion-exchanged product solution.

[0157] 45. The method of embodiment 44, wherein the ion exchange step comprises the use of an aqueous hydrochloric acid solution.

[0158] 46. ​​The ion exchange step is i. adding a volume of hydrochloric acid solution to the resulting solution to form an acidified solution; ii. passing the mercury through an ion exchange column containing an anion exchange resin pre-equilibrated with 0.15M HCl such that the mercury ions are adsorbed onto the anion exchange resin to form a reduced mercury solution containing dissolved product lanthanide, non-product lanthanide, and alkali metal ions; iii. passing a 0.15M HCl rinse through the ion exchange column after passing the acidified solution to collect the remaining amounts of product lanthanides, non-product lanthanides, and alkali metal ions in the ion exchange column; 46. ​​The method of embodiment 44 or 45, wherein the reduced mercury solution, the passed rinse, or a combination thereof is an ion exchange product solution.

[0159] 47. The hydrochloric acid solution is a concentrated aqueous HCl solution (about 11.5M); The anion exchange resin is a styrene-divinylbenzene resin, 47. The method of embodiment 46, wherein the rinse solution is a 0.15 M aqueous HCl solution.

[0160] 48. The method of embodiment 46 or 47, wherein the ion exchange product solution has a concentration of mercury that is 10 ppb or less.

[0161] 49. The method of any one of the preceding embodiments, further comprising performing a chromatographic separation of the ion-exchanged product solution to separate product lanthanides, non-product lanthanides, and alkali metal ions.

[0162] 50. i. loading the ion-exchanged product solution into a chromatography column containing a chromatography resin capable of adsorbing the product lanthanides and non-product lanthanides without adsorbing alkali metal ions, thereby adsorbing the product lanthanides and non-product lanthanides; ii. washing the packed chromatography column with a chromatography wash solution to remove alkali metal ions from the chromatography column without desorbing product and non-product lanthanides from the chromatography resin; iii. The method of embodiment 49, comprising passing the chromatography elution solution through a washed chromatography column having adsorbed product lanthanides and non-product lanthanides, wherein the product lanthanides and non-product lanthanides desorb from the chromatography resin and separate as they move through the column in the chromatography elution solution at different rates according to the respective partition coefficients of the column, thereby separating the product lanthanides and non-product lanthanides into a product lanthanide-containing eluate and a non-product lanthanide-containing eluate, respectively.

[0163] 51. The method of embodiment 50, wherein the chromatography resin comprises an alkyl derivative of phosphoric acid on an inert support.

[0164] 52. The method of embodiment 51, wherein the alkyl derivative of phosphoric acid is selected from the group consisting of di(2-ethylhexyl)orthophosphoric acid (HDEHP), 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (HEH[EHP]), and di-(2,4,4-trimethylpentyl)phosphinic acid (H[TMPeP]).

[0165] 53. The method of embodiment 50, wherein the chromatography resin comprises an alkyl phosphate alkyl ester on an inert support.

[0166] 54. The method of embodiment 50, wherein the chromatography resin comprises (2-ethylhexyl)phosphonic acid-(2-ethylhexyl)-ester (HEH[EHP]) on an inert support.

[0167] 55. The chromatographic wash solution is 0.15 M aqueous HCl; The chromatographic eluent is 1.4-1.5M aqueous HCl; 55. The method of any one of embodiments 50-54, wherein the chromatographic column is at a temperature in the range of about 40° C. to about 55° C. during the chromatographic separation process.

[0168] 56. The method according to any one of embodiments 49 to 55, wherein the ion exchange step is carried out before or after the chromatographic separation step.

[0169] 57. The method according to any one of embodiments 49 to 55, wherein the step of ion exchange is carried out before the step of chromatographic separation.

[0170] 58. The method of embodiment 57, wherein a chromatographic separation process further separates mercury within the ion-exchange product solution, thereby resulting in a product lanthanide-containing eluate having a mercury concentration that is 1 ppb or less.

[0171] 59. The method of embodiment 57 or 58, further comprising the step of reformulating the product lanthanide-containing eluate by heating the product lanthanide-containing eluate under an inert atmosphere to form a solid residue comprising the product lanthanide.

[0172] 60. The method of embodiment 59, wherein the product lanthanide in the solid residue is a product lanthanide chloride hydrate.

[0173] 61. The product lanthanide of the solid residue is 177 The method of embodiment 59, wherein LuCl3·nH2O.

[0174] 62. 177 62. The method of embodiment 61, wherein LuCl3·nH2O has a specific activity in the range of about 2775 GBq to about 4070 GBq / mg of Lu-177.

[0175] 63. The non-product lanthanide is reacted with the following steps: contacting the mercury cathode and the electrochemical cell with an acidic solution to extract the non-product lanthanide therein to form a non-product lanthanide-containing solution; precipitating the non-product lanthanide from the purified non-product lanthanide-containing solution with oxalic acid to form a non-product lanthanide oxalate; and 63. The method of any one of the preceding embodiments, further comprising recovering the non-product lanthanide oxalate salt by heating to form recovered non-product lanthanide oxide.

[0176] 64. Non-product lanthanide oxalate is 176 Yb2(O x ) 3 and the recovered non-product lanthanide oxide is 176 64. The method of embodiment 63, wherein the Yb2O3 is Yb2O3.

[0177] 65. Product lanthanides, preferably non-carrier-added (nca) product lanthanide solutions, more preferably nca 177 1. A method for producing a solution of Lu, the method comprising: providing a mixture comprising a product lanthanide and a non-product lanthanide; Separating the product lanthanide and non-product lanthanides according to any one of embodiments 49 to 64; After the chromatographic separation step, the eluate containing the product lanthanide is concentrated in an inert atmosphere; Product lanthanide, preferably a non-carrier added (nca) product lanthanide solution, more preferably an nca 177 A method for recovering a solution containing Lu.

[0178] 66. The recovered solution containing the product lanthanide, preferably the non-carrier-added (nca) product lanthanide, is greater than 98% non-carrier-added (nca) product lanthanide, preferably greater than 99% nca 177 66. The method of embodiment 65, comprising Lu.

[0179] 67. The recovered solution containing the product lanthanide, preferably the non-carrier-added (nca) product lanthanide, is more than 98% non-carrier-added (nca) product lanthanide, preferably more than 99% nca having a specific activity of ≧2900 GBq / mg. 177 67. The method of embodiment 65 or 66, comprising Lu.

[0180] 68. The method of any one of embodiments 65-67, wherein the method comprises providing about 0.5-10 g and about 555 GBq-15000 GBq of a mixture of product and non-product lanthanides.

[0181] 69. The mixture of product radioactive lanthanides and non-product lanthanides is irradiated with neutrons. 176 Yb, preferably ytterbium oxide, is applied to a target to produce a radioisotope 177 Yb is produced and the target decays after beta decay. 177 From Yb 177 69. The method of any one of embodiments 66-68, wherein Lu is generated by:

Claims

1. 1. A method for separating product and non-product lanthanides in a mixture, comprising: separating said product and non-product lanthanides by electrolyzing said mixture while controlling the pH of said mixture in the range of about 6.0 to about 7.0 by adding a base during electrolysis of said mixture; the base is an alkali metal hydroxide; The pH control is periodic or continuous; and The method, wherein electrolyzing the mixture comprises dissolving the product lanthanides and the non-product lanthanides present in the mixture with a trifluoromethanesulfonic acid solution, a mercury cathode, and an anode.

2. The product lanthanide is lutetium; the non-product lanthanide is ytterbium; the base is selected from the group consisting of lithium hydroxide, sodium hydroxide, and potassium hydroxide; the trifluoromethanesulfonic acid solution has a concentration of 2M to 4M; The pH is controlled at about 6.5; the mercury cathode has a surface area of ​​40 to 120 cm 2 , and electrolyzing the mixture further comprises stirring the mercury cathode at a speed of 200 to 400 rpm; and the anode comprises a metal selected from the group consisting of ruthenium, palladium, osmium, iridium, platinum, and alloys or combinations thereof; The method of claim 1.

3. The product lanthanide is 177 Lu; the non-product lanthanide is 176 Yb; the base is lithium hydroxide, the trifluoromethanesulfonic acid solution has a concentration of 3 M to 3.5 M; The pH is controlled at about 6.5; the mercury cathode has a surface area of ​​75 to 85 cm 2 , and electrolyzing the mixture further comprises stirring the mercury cathode at a speed of 280 to 300 rpm; and The anode is platinum. The method of claim 1.

4. A method for producing a lithium citrate-containing electrolyte solution, comprising the steps of: pre-electrolysis of an initial electrolyte solution comprising lithium citrate, wherein at least a portion of the lithium ions of the lithium citrate of the initial electrolyte solution are reduced; a step of ion exchange carried out using an anion exchange resin after electrolysis of said mixture; a chromatographic separation step carried out before or after said ion exchange step, said chromatographic separation step comprising only one chromatographic column or two chromatographic columns connected in parallel; The method of claim 1 further comprising:

5. 1. A method for separating product and non-product lanthanides in a mixture by electrolysis, the method comprising a step of preliminary electrolysis, in which an initial electrolyte solution containing an alkali metal salt and free of product and non-product lanthanides is adjusted by electrolysis so that at least a portion of the alkali metal ions of the alkali metal salt of the initial electrolyte solution are reduced and amalgamated at the mercury cathode, the alkali metal salt being lithium citrate and the alkali metal ions being lithium ions.

6. The product lanthanide is lutetium; the non-product lanthanide is ytterbium; the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.15 M to about 0.90 M; the mercury cathode has a surface area of ​​40 to 120 cm 2 ; The method of claim 5.

7. The method of claim 1, wherein the product lanthanide is 177 Lu; the non-product lanthanide is 176 Yb; the mixture has a radioactivity of at least 185 GBq; the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.40 M to about 0.60 M; and the mercury cathode has a surface area of ​​75 to 85 cm 2 ; The method of claim 5.

8. 6. The method of claim 5, wherein the product lanthanides and the non-product lanthanides in the mixture are derived from an irradiated target comprising the mixture as an oxide, the irradiated target having a mass in the range of about 0.5 g to about 10 g and a radioactivity in the range of about 555 Gbq to about 15,000 Gbq.

9. The electrolysis of the mixture comprising: dissolving the product lanthanide and the non-product lanthanide in the mixture with trifluoromethanesulfonic acid; controlling the pH of the mixture in the range of about 6.0 to about 7.0 by adding a base during electrolysis of the mixture; and Stirring the mercury cathode at a speed of 200 to 400 rpm. The method of claim 5 further comprising:

10. The method of claim 1, further comprising the step of ion exchange using an anion exchange resin after electrolysis of the mixture; a chromatographic separation step before or after said ion exchange step, The method of claim 5 further comprising:

11. 1. A method for separating product lanthanides and non-product lanthanides in a mixture, said method comprising: a. providing an electrochemical cell, said electrochemical cell comprising: i. mercury cathode, ii. an anode; and iii. providing an initial electrolyte solution comprising alkali metal ions from an alkali metal salt dissolved in an initial solvent comprising water, the initial electrolyte solution being in contact with the mercury cathode and the anode; b. adding a second solution to the initial electrolyte solution in the electrochemical cell to form a separate electrolyte solution in contact with the mercury cathode and the anode, the second solution comprising: i. a mixture comprising the product lanthanide and the non-product lanthanide; ii. forming a second solvent capable of dissolving the mixture including the product lanthanide and the non-product lanthanide without reacting with the anode and the mercury cathode; c. separating the non-product lanthanide from the separated electrolyte solution, said separating comprising operating the electrochemical cell to: i. reducing the oxidation state of at least a portion of the non-product lanthanides; ii. amalgamating the reduced non-product lanthanide with the mercury of the mercury cathode; and iii. Separating, including recovering a product solution containing the dissolved product lanthanide; This separates the product lanthanides as well as the non-product lanthanides.

12. The surface area of ​​the cathode is refreshed while operating the electrochemical cell to separate the non-product lanthanides from the separating electrolyte solution, and the surface area of ​​the cathode is refreshed by flowing the mercury of the mercury cathode such that the mercury at or near its interface with the separating electrolyte solution is transported away from the interface prior to the formation of a layer of reaction product(s) extending from the interface into the volume of the mercury cathode, and the layer inhibits the reduction of the oxidation state of the non-product lanthanides and / or amalgamation of the reduced non-product lanthanides; the electrochemical cell includes a flow device for flowing the mercury in the mercury cathode, the flow device being configured and operative to flow the mercury to refresh the surface area of ​​the cathode without disturbing amalgamated solids at the bottom of the mercury cathode; The method of claim 11.

13. the product lanthanide is lutetium; the non-product lanthanide is ytterbium; the mercury in the provided mercury cathode is at least about 99% pure; the cathode has a surface area ranging from about 40 cm 2 to about 120 cm 2 ; the anode comprises a metal selected from the group consisting of ruthenium, rhodium, palladium, osmium, iridium, platinum, and alloys, mixtures, or combinations thereof; the anode has a surface area ranging from about 10 cm 2 to about 40 cm 2 ; the initial electrolyte solution has an alkali metal ion concentration in the range of about 0.15 M to about 0.90 M; the alkali metal ion is a lithium ion, the alkali metal salt is lithium citrate; the second solvent is a trifluoromethanesulfonic acid solution having a concentration ranging from about 2 M to about 4 M; step (c) comprises operating the electrochemical cell under an inert atmosphere with the cathode flowing at a separation pH ranging from 6.0 to 7.0, a separation temperature ranging from about 10° C. to about 30° C., a separation potential ranging from about 5 V to about 10 V, and a separation current ranging from about 1 ampere to about 4 amperes for a separation duration ranging from about 0.5 hours to about 4 hours; said separating step (c) being a single continuous operation of said electrochemical cell until at least 90% of said non-product lanthanides in said separated electrolyte solution are reduced and amalgamated with said mercury at said mercury cathode; 12. The method of claim 11, wherein the product solution containing the dissolved product lanthanide contains 20 ppm or less of mercury.

14. the product lanthanide being １７７ Lu, the non-product lanthanide is １７６ Yb, The mercury in the provided mercury cathode is about 99.999% pure; the cathode has a surface area ranging from about 75 cm 2 to about 85 cm 2 ; the anode comprises platinum; The anode is about 25 cm ２ ~Approx. 35cm ２ and having a surface area in the range of the initial electrolyte solution having an alkali metal ion concentration in the range of about 0.40 M to about 0.60 M; the alkali metal ion is a lithium ion, the alkali metal salt is lithium citrate; the second solvent is a trifluoromethanesulfonic acid solution having a concentration ranging from about 3 M to about 3.5 M; step (c) comprising operating the electrochemical cell under an inert atmosphere with the cathode flowing at a separation pH of about 6.5, a separation temperature ranging from about 15° C. to about 25° C., a separation potential of about 8 V, and a separation current of about 2.5 amperes for a separation duration ranging from about 1.5 hours to about 2.5 hours; the separating step (c) is a single continuous operation of the electrochemical cell until at least 99% of the non-product lanthanides in the separated electrolyte solution are reduced and amalgamated with the mercury at the mercury cathode; the product solution containing the dissolved product lanthanides contains 20 ppm or less of mercury; The method of claim 11.

15. The method further comprises conditioning the provided electrochemical cell before adding the second solution to the initial electrolyte solution, wherein conditioning the provided electrochemical cell comprises reducing the oxidation state of at least a portion of the alkali metal ions in the initial electrolyte solution and amalgamating the reduced alkali metal with the mercury of the mercury cathode such that the mercury cathode additionally comprises alkali metal amalgam; conditioning the provided electrochemical cell comprises operating the electrochemical cell under an inert atmosphere with the cathode flowing at a controlled pH in the range of about 6.0 to about 7.0, a controlled temperature in the range of about 10°C to about 30°C, a controlled potential in the range of about 5V to about 10V, and a controlled current in the range of about 1 ampere to about 4 amperes for a controlled duration in the range of about 0.5 hours to about 2 hours; The method of claim 11.

16. the adjusted pH during the adjusting, the separated pH during separation step (c), the adjusted pH, and the separated pH are controlled via periodic or continuous addition of a lithium hydroxide solution; the inert atmosphere is an argon purge at about atmospheric pressure for at least 30 minutes immediately prior to conditioning the cathode; Immediately after the conditioning step, the cathode comprises a reduced alkali metal concentration relative to the mercury in a range of from about 50 ppm to about 1,000 ppm.

16. The method of claim 15.

17. the mixture containing the product lanthanide and the non-product lanthanide is from an irradiated target containing the mixture as an oxide, the irradiated target having a mass in the range of about 0.5 g to about 10 g and an activity in the range of about 555 Gbq to about 9250 Gbq; further comprising dissolving the irradiated target containing the mixture including the product lanthanide and non-product lanthanide as oxides in the second solvent in a dissolution vessel; the step of adding the second solution to the initial electrolyte solution comprises adding the contents of the dissolution vessel to the initial electrolyte solution; the second solution having a mass ratio of non-product lanthanide to product lanthanide in the range of about 1,000:1 to about 4,000:1; The method of claim 11.

18. further comprising rinsing the dissolution vessel with a volume of a rinse solution, the rinse solution being an aqueous lithium citrate solution; 20. The method of claim 17, wherein the step of adding the second solution to the initial electrolyte solution further comprises adding the volume of the rinse solution used to rinse the dissolution vessel to the initial electrolyte solution.

19. contacting the dissolved product lanthanides with an anion exchange resin, thereby reducing dissolved mercury in the product solution; 12. The method of claim 11, further comprising the step of ion exchanging the product solution, including recovering the ion-exchanged product solution.

20. the ion exchange step adding a volume of hydrochloric acid solution to the resulting solution to form an acidified solution; passing the acidified solution through an ion exchange column containing the anion exchange resin such that mercury ions are adsorbed onto the anion exchange resin to form a reduced mercury solution containing dissolved product lanthanides, non-product lanthanides, and alkali metal ions; and passing a rinse through the ion exchange column after the passage of the acidified solution to collect the product lanthanide, non-product lanthanide, and alkali metal ion remaining in the ion exchange column; 20. The method of claim 19, wherein the reduced mercury solution, the passed rinse, or a combination thereof is the ion-exchanged product solution, and the ion-exchanged product solution has a concentration of mercury that is 10 ppb or less.

21. the hydrochloric acid solution is 11.5 M aqueous HCl; the anion exchange resin is a styrene-divinylbenzene resin, 21. The method of claim 20, wherein the rinse solution is a 0.15 M aqueous HCl solution.

22. 20. The method of claim 19, further comprising performing a chromatographic separation of the ion-exchanged product solution to separate product lanthanides, non-product lanthanides, and alkali metal ions.

23. the chromatographic separation comprising: loading the ion-exchanged product solution into a chromatography column containing a chromatography resin capable of adsorbing the product lanthanides and non-product lanthanides without adsorbing alkali metal ions, thereby adsorbing the product lanthanides and non-product lanthanides; washing the packed chromatography column with a chromatography wash solution to remove alkali metal ions from the chromatography column without desorbing product and non-product lanthanides from the chromatography resin; 23. The method of claim 22, comprising passing a chromatography elution solution through the washed chromatography column having adsorbed product lanthanides and non-product lanthanides, wherein the product lanthanides and non-product lanthanides desorb from the chromatography resin and separate as they move through the column in the chromatography elution solution at different rates according to their respective distribution coefficients, thereby separating the product lanthanides and non-product lanthanides into a product lanthanide-containing eluate and a non-product lanthanide-containing eluate, respectively.

24. the chromatography resin comprises an alkyl derivative of phosphoric acid on an inert support, the alkyl derivative of phosphoric acid being selected from the group consisting of di(2-ethylhexyl)orthophosphoric acid (HDEHP), 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (HEH[EHP]), and di-(2,4,4-trimethylpentyl)phosphinic acid (H[TMPeP]); the chromatography wash solution is 0.15 M aqueous HCl; the chromatography elution solution is 1.4-1.5M aqueous HCl; the chromatographic column is at a temperature ranging from about 40° C. to about 55° C. during the chromatographic separation process; 24. The method of claim 23.

25. the ion exchange step is carried out before the chromatographic separation step, 23. The method of claim 22, wherein the chromatographic separation process further separates mercury within the ion-exchange product solution, thereby resulting in the product lanthanide-containing eluate having a mercury concentration that is 1 ppb or less.

26. 26. The method of claim 25, further comprising the step of reformulating the product lanthanide-containing eluate by heating the product lanthanide-containing eluate under an inert atmosphere to form a solid residue containing the product lanthanide, wherein the product lanthanide in the solid residue is 177 LuCl 3 .nH 2 O having a specific activity ranging from about 2900 GBq / mg Lu to about 4070 GBq / mg Lu.

27. The non-product lanthanides are separated by the following steps: contacting the mercury cathode and the electrochemical cell with an acidic solution to extract non-product lanthanides therein to form a non-product lanthanide-containing solution; precipitating the non-product lanthanide from the purified non-product lanthanide-containing solution with oxalic acid to form a non-product lanthanide oxalate; and 12. The method of claim 11, further comprising recovering the non-product lanthanide oxalate by heating to form recovered non-product lanthanide oxide.

28. the non-product lanthanide oxalate １７６ Yb ２ (O ｘ ) ３ and the recovered non-product lanthanide oxide is １７６ Yb ２ O ３ 28. The method of claim 27, wherein:

29. A method for producing a non-carrier added (n.c.a.) product lanthanide solution, said method comprising: providing a mixture comprising a product lanthanide and a non-product lanthanide; separating the product and non-product lanthanides according to the method of claim 23; After the chromatographic separation step, the eluate containing the product lanthanide is concentrated in an inert atmosphere; The method recovers the non-carrier added (n.c.a.) product lanthanide solution.

30. The mixture of product and non-product lanthanides is subjected to neutron irradiation of a target of ytterbium-176 oxide to produce radioactive isotopes. １７７ Yb is produced, and the target decays after beta decay to １７７ From Yb １７７ and allowing Lu to be generated, the mixture is about 0.5 to 10 g and about 555 GBq to 15,000 Gbq; and The non-carrier added (n.c.a.) product lanthanide is greater than 99% n.c.a. 177 Lu with a specific activity of ≥ 2900 GBq / mg Lu; 30. The method of any one of claims 29.

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