Methods and systems for separation and concentration of radium utilizing manganese oxide

Abstract

Disclosed are systems and methods for separation and / or concentration of radium. In an example, a chromatography resin may be utilized to separate radium from a volume, and then the radium may be eluted from the resin with a chelating agent. The resulting eluent volume may then be further concentrated into a smaller volume using a solid oxidant resin (such as MnO2) in a packed column. Once eluted from the MnO2, the resulting eluent volume may have a volume orders of magnitude lower than the original radium volume. In other examples as disclosed, the chelated radium eluent volume may be allowed to generate actinium, a daughter isotope of radium. The aged volume may then be concentrated using the MnO2.

Description

P100172-WO-SEC1-25TPI / 19879.0015WOU1METHODS AND SYSTEMS FOR SEPARATION AND CONCENTRATION OF RADIUM UTILIZING MANGANESE OXIDECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 781,830, filed April 1, 2025, which is incorporated by reference herein in its entirety .BACKGROUND

[0002] Current processes for generating and harvesting actinium (hereinafter ”Ac". for example, Ac-225) from radium (hereinafter “Ra?’. for example, Ra-225) may include passing the stream or volume including the Ra through a chromatography column for the separation of the Ac from the Ra, the latter remaining behind in the column (bound to the resin) as the former is eluted out of the column. The column environment can then function as a liquid generator, and the remaining, bound Ra may then generate additional Ac, which can be further eluted out of the column.

[0003] One potential resin that has been historically tested as a liquid generator is MRT-20. However, experimental data illustrates that binding and storage of the Ra onto the MRT-20 resin may cause radiolytic damage as well as loss of both Ra and Ac during washing / elution steps. Over time, as the column is eluted for Ac, the percentage of Ra breakthrough, as well as the percentage of Ac recovered, varies and remains outside of desired levels.

[0004] Methods of Ac-225 production (for example, generation from thorium (hereinafter 'Th", for example, Th-229), irradiation of Ra (for example, Ra-226), spallation of Th (for example, Th-232), and other methods) may depend on efficiently utilizing Ra in an aqueous form. Several methods for Ac-225 separations have reported using an organic chelator, such as ethylenediaminetetraacetic acid, (hereinafter “EDTA”), which may be removed by acidifying and / or ion exchange (also referred to as ‘TEX”) chromatography. However, the use of organic resins with alpha-emitting radionuclides can cause radiolytic breakdown of the resin which requires downstream processing such as digestion with H2O2 or use of a prefilter (resin support material) column to remove.P100172-WO-SEC1-25TPI / 19879.0015WOU1METHODS AND SYSTEMS FOR SEPARATION AND CONCENTRATION OF RADIUM UTILIZING MANGANESE OXIDE

[0005] Disclosed herein are systems and methods for separation and / or concentration of radium. In an example, a chromatography resin may be utilized to separate radium from a volume, and then the radium may be eluted from the resin with a chelating agent. The resulting eluent volume may then be further concentrated into a smaller volume using a solid oxidant resin (such as MnCL) in a packed column. Once eluted from the Mn02, the resulting eluent volume may have a volume orders of magnitude lower than the original radium volume. In other examples as disclosed herein, the chelated radium eluent volume may be allowed to generate actinium, a daughter isotope of radium. The aged volume may then be concentrated using the M11O2.

[0006] This summary is provided to introduce a selection of methods and compositions in a simplified form that are further described below7in the Detailed Description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Various aspects of at least one example are discussed below7with reference to the accompanying figures, which are not intended to be drawn to scale. The figures are included to provide an illustration and a further understanding of the various aspects and examples and are incorporated in and constitute a part of this specification but are not intended as a definition of the limits of a particular example. The drawings, together with the remainder of the specification, serve to explain principles and operations of the described and claimed aspects and examples. In the figures, each identical or nearly identical component that is illustrated in various figures is represented by a like numeral. For purposes of clarify, every7component even when illustrated may not be expressly labeled in every figure. Non-limiting and non-exhaustive examples are described with reference to the following Figures.

[0008] Figure 1 illustrates an example system for generating an Ac volume.

[0009] Figure 2 illustrates an example system for capturing an Ra volume.

[0010] Figure 3 illustrates an example method and example operational diagrams for capturing Ra from an initial volume.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0011] Figure 4 illustrates an example method for determining isotope retention at various conditions.

[0012] Figure 5 illustrates an example elution profile of Ra-225 from MRT using 0.05 M EDTA at a pH of 10-11 collected in single bed volume fractions.

[0013] Figure 6 illustrates an example elution profile of Ra-225 from MnCh using 5 M and 8 M HNOs collected in single bed volume fractions.

[0014] Figure 7A illustrates an example yield of Ac-225 radiolabeling with DOTA showing greater than 99% incorporation, by Free Ac-225.

[0015] Figure 7B illustrates an example yield of Ac-225 radiolabeling with DOTA showing greater than 99% incorporation, by DOTA / Ac 3800:1.

[0016] Figure 8 illustrates example percent recovery of Ra and Ac from Mn02 in in bed volumes of a first elution.

[0017] Figure 9 illustrates example percent recovery of Ra from Mn02 in bed volumes of a second elution.

[0018] Figure 10 illustrates example Ra yield from each fraction / step for Example 7.

[0019] Figure 11 illustrates example Ra yield from each fraction / step for Example 8.

[0020] Figure 12 illustrates example Ra yield from each fraction / step for Example 9.DETAILED DESCRIPTION

[0021] In the following detailed description, references are made to the accompanying drawings that form a part hereof, and in which are shown by way of illustrations specific embodiments or examples. These aspects may be combined, other aspects may be utilized, and structural changes may be made without departing from the present disclosure. Examples may be practiced as methods, systems, or devices. The following detailed description is therefore not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims and their equivalents.

[0022] Before the disclosed designs and operational concepts are disclosed and described, it is to be understood that this disclosure is not limited to the particular structures, process steps, or materials disclosed herein, but is extended to equivalents thereof as would be recognized by those ordinarily skilled in the relevant arts. It should also be understood that terminology employed herein is used for the purpose of describing particular embodiments of the nuclear reactor only and is not intended to be limiting. It must be noted that, as used in this specification, the singular forms "a,"P100172-WO-SEC1-25TPI / 19879.0015WOU1"an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a lithium hydroxide" or “a chloride salt” is not to be taken as quantitatively or source limiting, reference to "a step" or “an operation” may include multiple steps or operations, reference to "producing" or "products" of a reaction should not be taken to be all of the products of a reaction, and reference to "reacting" may include reference to one or more of such reaction steps. As such, the step of reacting can include multiple or repeated reaction of similar materials to produce identified reaction products.

[0023] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term "about.” The term “about” when used herein in connection with numerical values means ± 20% and with percentages means ±5% (for example, “about 100%” would be read to mean 95% to 105%).

[0024] As used herein, the term “comprising” refers to a composition, compound, formulation, or method that is inclusive and does not exclude additional elements or method steps.

[0025] As used herein, the term “consisting of’ refers to a compound, composition, formulation, or method that excludes the presence of any additional component or method steps.

[0026] Current processes for generating and harvesting actinium (hereinafter “Ac”, for example, Ac-225) from radium (hereinafter “Ra”, for example, Ra-225) may include passing the stream or volume including the Ra through a chromatography column for the separation of the Ac from the Ra, the latter remaining behind in the column (bound to the resin) as the former is eluted out of the column. The column environment can then function as a liquid generator, and the remaining, bound Ra may then generate additional Ac. which can be further eluted out of the column.

[0027] One potential resin that has been historically tested as a liquid generator is MRT-20. However, experimental data illustrates that binding and storage of the Ra onto the MRT-20 resin may cause radiolytic damage as well as loss of both Ra and Ac during w ashing / elution steps. Over time, as the column is eluted for Ac, the percentage of Ra breakthrough, as well as the percentage of Ac recovered, varies and remains outside of desired levels.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0028] Disclosed herein are methods and systems wherein MRT-20 resin is used unexpectedly and advantageously to separate and / or concentrate Ra. For example, once loaded onto the MRT-20 resin, instead of remaining bound to the resin as a generator, the Ra may be eluted from the resin with a chelating agent (for example, 0.05 M EDTA) having a pH of between about 10-11. The resulting output volume may then be further concentrated into a smaller volume using a solid oxidant (such an manganese oxide, also referred to as manganese dioxide, hereinafter “Mn02”) resin. Once eluted from the Mn02, the resulting eluent volume may have a volume orders of magnitude lower than the original volume of the Ra volume fed to the MRT-20 resin. For example, a reduction in volume from about 1.88 L to about 100 mL of volumes having a concentration of between about 5-8 M nitric acid (hereinafter “HNOs”) may be achieved, in some examples. The disclosed methods therefore reduce concern of loss of Ra-225 from inconsistent column behavior over time from damaged MRT-20, and additionally provide Ra-225 at a smaller processing volume (further eliminating or reducing need for other concentrating operations, such as evaporation or particulate formation / filtration).

[0029] Disclosed herein are methods and systems for the use MnCh (sometimes referred to herein as MnCh resin) in an inorganic chromatographic-based separation of Ra and / or Ac from EDTA in an aqueous volume which can provide Ac suitable for large-scale production by reducing the volume and being suitable for radiolabeling.

[0030] As shown by the examples herein, Gamma spectroscopy analysis by High-Purity Germanium (HPGe) indicated that 99% of Ra-225 after decay correction was recovered from the MnCh column, separated from EDTA. This Ra-225 could then be used for Ac-225 production, unaffecting its radiolabeling capability after downstream polishing steps. Radiolabeling was tested with DOTA (dodecane tetraacetic acid, also “tetraxetan”) (1900:1 DOTA:Ac) in 0.2 MNH4OAC at a pH of between 5.5-6 at 15 min at 85 °C and measured by TLC, showing 99% incorporation after 24 hr. Excess Mnx+(theorized to be 2+) was quantitively removed indicated by trace metal analysis which was conducted on the free Ac-225 using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). This method demonstrates the ability to use MnCh resin for concentrad on of an aqueous solution of Ra-225 and / or Ac-225 complexed with EDTA, while keeping everything in solution without having to evaporate or form and filter precipitates.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0031] Also disclosed herein are methods for utilizing the MnCh as a Ra-225 generator for Ac-225 production. In these methods of isolating Ra-225, co-elution of Mnn+(where n is likely 2) should be removed. We show that Lanthanide resin (hereinafter ‘'LN resin”), for example, available from Eichrom, may separate Mn2+and / or other divalent metals from Ac-225. LN resin is composed of a polymer-based resin modified with Di(2-ethylhexyl)phosphoric acid (HDEHP). In some examples, LN resin may also separate Mn4+from Ac-225 and / or Ra-225.

[0032] Liquid chromatography as discussed herein is often used in the separation of one or more substances (e.g. solutes) from a solution. Generally, chromatography includes loading a solution containing several substances in a solvent (sometimes called the mobile phase) into a column that is packed with a solid (often a resin, sometimes called the stationary phase). The solution passes through column either under gravity or via imposition of a differential pressure. The solid (e.g. resin) is selected such that the various substances of the solution pass differently through the column. In some t pes of chromatography, the substances pass through the solid at a different rate, and are thus separated as different “peaks” or “bands” that exit the column at different times as a number of solvent washes is passed through the column. In some types of chromatography, the substances have a different affinity for the solid (e.g. resin). For example, a first substance may become attached to (for example, adsorbed to, covalently or ionically attached to, or covalently bound to) the solid, while the other substance(s) pass through the column without becoming attached to the solid. In some cases, a number of additional solvent washes may be passed through the column after the initial loading to wash as much of the other substances out. Then, the first substance is released from the solid by passing at least one wash solution through the column (also called eluting the column), often with a wash solution that has a specific pH, ionic strength, molarity, or other property that removes the first substance from the solid. In many examples, wash / eluent volumes may include a plurality of wash / eluent fractions, which are provided to / through the column consecutively until a desired condition is reached (for example, a desired concentration or lack thereof of a particular substance in the outlet solution). For a particular substance (e.g. solute), a capacity factor (k‘) can be calculated that relates to the retention of the substance on the particular solid (e.g. resin). A higher capacity factor indicates a greater retention of theP100172-WO-SEC1-25TPI / 19879.0015WOU1substance on the solid (for example, depending on the ty pe of chromatography: a stronger bond withstanding washing, or a longer retention time in the solid phase).

[0033] In some examples, the designs disclosed herein may be utilized in test, pilot, or commercial -scale systems, including benchtop and larger.

[0034] These and other examples will be explained in more detail below with respect to the Figures. Although the Figures and Examples discussed herein utilize examples of Ra and Ac including Ra-225 and Ac-225, similar processes may be applicable to other radioisotopes (e.g. other isotopes of Ra and / or Ac) and are contemplated. The disclosed methods and systems may be applicable to various isotopes of Ra and Ac. For example, Ramay include one or more of Ra-225, Ra-226, Ra-223, Ra-224, Ra-228, and / or others. For example. Ac may include one or more of Ac-225, Ac-228, Ac-227, and / or others.

[0035] FIG. 1 illustrates an example system 100 for generating an Ac volume. A generator column 102 that includes Th may generate, as an output, a volume VI that contains Ac and Ra. In examples, the Th is Th-229, the Ra is Ra-225, and the Ac is Ac-225. In some examples, generator column 102 may include a resin such as AG MP-1M (for example, which may be obtained from BioRad Laboratories, Inc., 1000 Alfred Nobel Drive, Hercules, California 94547). In examples, within the generator column 202, Th-229 will subsequently decay over time to generate its daughter products, including Ra-225 and Ac-225. As the Th decays, the generated Ac-225 (and, in some examples, at least some Ra-225) is washed from the generator column 102 by passing a wash volume through the generator column 102, forming volume VI.

[0036] In examples, volume VI contains an acid (for example, HNO3, HC1 (hydrochloric acid), NaNCh (sodium nitrate), HOA (acetic acid), and / or NaOA (sodium acetate), or others). In some examples, the makeup solvent of VI may include water and / or another aqueous solvent (in addition to the acid at a particular concentration, for example). In some examples, reconstituted Th that escapes the generator column 102 may be captured from volume VI by passing volume VI through a thorium capturing column or columns (not shown) and returned as volume V2 to a feed volume F of the generator column 102.

[0037] Volume VI is received at an inlet of an extraction chromatography column 104. Extraction chromatography column 104 may have a body defining an interior chamber that contains an extraction chromatography resin. In some examples, theP100172-WO-SEC1-25TPI / 19879.0015WOU1extraction chromatography resin is N,N,N’,N'-tetra-n-octyldiglycolamide (DGA Resin, Normal, herein nDGA") and / or N,N,N',N’-tetra-2-ethylhexyldiglycolamide (DGA Resin, Branched, herein '‘bDGA”) resin, both available from Eichrom Technologies, Inc., 1955 University Lane, Lisle, IL, 60532. At the extraction chromatography column 104, the volume VI is passed through the extraction chromatography column 104 and contacts the resin therein. The Ac from volume VI is retained within the interior chamber (e.g. is loaded onto the extraction chromatography resin) and the remainder of the volume VI passes through the extraction chromatography column 104 to form a dilute Ra volume V3 that is removed from the extraction chromatography column 104. In examples, the extraction chromatography resin may include one or more other appropriate resins with affinity’ for Ac.

[0038] Dilute Ra volume V3 may include Ra, some Ac, some Th, and / or other components. Dilute Ra volume V3 may be processed (for example, concentrated and / or separated as described in FIG. 2) at a downstream Ra-processing system 108. In some examples, Ra-processing system 108 may separate Ra from other components of the dilute Ra volume V3 that form the waste volume of the Ra-separation process, although the other components may be further utilized. For example, Ra-processing system 108 may separate the Ra from Ac, the latter of which may be recovered and combined with Ac generated by extraction chromatography column 104 or a further downstream Ac processing column 106. In examples, Ra-processing system 108 may separate the Ra from Th, the latter of which may be recovered and reconstituted for feeding back into the generator column 102. In examples, Ra-processing system 108 may separate the Ra from Th and / or Ac. or may simply concentrate Ra, and the Ra may¬ be recovered and reconstituted for feeding back into the extraction chromatography column 104 (for example, as recovered Ra volume V9). In some examples, Ra-processing system 108 may include at least one extraction chromatography column including a resin that binds to Ra and / or divalent metals, enabling the separation of divalent metals from the dilute Ra volume V3. In particular examples, system 108 may include the systems as described in FIG. 2.

[0039] In examples, the Ac retained on the resin within the extraction chromatography column 104 is eluted from the extraction chromatography resin and is removed from the extraction chromatography column 104 within an Ac volume or eluent / eluted volume V4. The input of the wash / eluent fluid into any columns is notP100172-WO-SEC1-25TPI / 19879.0015WOU1shown in FIG. 1 but the reader will understand that after the loading of a column with whatever material it extracts from a first volume, that extracted material is later removed by the input of the wash / eluent fluid in a separate, distinct step. In some examples, elution is performed by passing a wash / eluent fluid containing an acid or other compound (for example, H2O2, HNO3, HC1, NaNCh, HO A, and / or NaO A, or others) through the extraction chromatography column 104, thereby releasing the Ac from the resin and forming Ac volume V4. In some examples, the makeup solvent of V4 (and / or the wash / eluent fluid) may include water and / or another aqueous solvent (in addition to the acid at a particular concentration, for example).

[0040] In some examples, the Ac volume V4 is received at one or more operations of a first polishing system 118. First polishing system 118 may include one or more columns or other means of separation, as well as supporting equipment such as valves, ports, filters / pre-filters, and others. In examples, first polishing system 118 includes a dow nstream Ac processing column 106. Column 106 may include a column body that defines an interior chamber that contains an Ac-retaining resin. In some examples, the Ac-retaining resin may include a UTEVA resin, which may be obtained from Eichrom Technologies, Inc., 1955 University Lane, Lisle, IL, 60532, or another suitable resin type.

[0041] In a particular example, first polishing system 118 may include a column 106 containing a UTEVA-containing resin, upstream of a second column (not pictured) that contains a bDGA resin (for examples, such a column having similar properties to extraction chromatography column 104), the bDGA-containing column being followed by at least one filter.

[0042] In some examples, Ac volume V4 is passed through the Ac processing column 106 and contacts the resin therein. The Ac from volume V4 is retained within the interior chamber (e.g. is loaded onto the resin therein) and the remainer of volume V4 passes through the column to form volume V5. In some examples, the outlet volume V5 of the first polishing system 118 may include residual Ra, Th, and / or other compounds of the volume V4, which may be further separated and / or disposed of at residual processing system 110. In examples, the Ac retained on the resin within the Ac processing column 106 is eluted from the Ac-retaining resin of column 106 and is removed from first polishing system 118 as a concentrated Ac volume or eluent / eluted volume V6. In some examples, elution is performed by passing a wash / eluent fluidP100172-WO-SEC1-25TPI / 19879.0015WOU1containing an acid or other compound (for example, H2O2, HNO3, HC1, NaNCh. HO A, and / or NaOA, or others) through the Ac processing column 106, thereby releasing the Ac from the resin and forming volume V6. In some examples, the makeup solvent of V6 (and / or the wash / eluent fluid) may include water and / or another aqueous solvent (in addition to the acid at a particular concentration, for example).

[0043] In some examples, the Ac volume V6 is received at one or more operations of a second polishing system 120. Second polishing system 120 may include one or more columns or other means of separation, as well as supporting equipment such as valves, ports, filters / pre-filters, and others. In examples, second polishing system 120 includes an Ac polishing column 112. Polishing column 112 may include a column body that defines an interior chamber that contains a resin that, retains Ac under some conditions and that retains one or more target impurities under some conditions.

[0044] In some examples, volume V6 is passed through the Ac polishing column 112 and contacts the resin therein. The Ac from V6, as well as some may be retained within the interior chamber (e.g. is loaded onto the resin therein) and the remainer of volume V6 passes through the column to form volume V7. In some examples, one or more other wash volumes may be passed through the Ac polishing column 112; these other w ash volumes may release impurities from the resin and form an outlet volume (for example, similar to volume V7). In some examples, the outlet volume V7 (and other outlet streams) may include impurities) of the Ac volume V6, which may be further separated and / or disposed of at residual processing system 114, in some examples.

[0045] In examples, the retained Ac retained on the resin within the Ac polishing column 112 is eluted from the resin of Ac polishing column 112 and is removed from second polishing system 120 as an (eluent / eluted) Ac product volume V8. In some examples, elution is performed by passing a wash fluid containing an acid or other compound, (for example, H2O2, HNO3, HC1, NaNCh, HO A, and / or NaOA, or others) through the Ac polishing column 112, thereby releasing the Ac from the resin and forming product volume V8. In some examples, Ac product volume V8 has a pH in a commercially acceptable range for downstream (e.g. medical, pharmaceutical) uses. In examples, the Ac product volume purity7is suitable for downstream radiolabeling (for examples, for the formation of radiopharmaceuticals or radiotracers). In someP100172-WO-SEC1-25TPI / 19879.0015WOU1examples, the Ac product volume V8 may be further concentrated, separated, and / or otherwise processed, transported, or utilized at downstream systems 116.

[0046] FIG. 2 illustrates an example system 200 for capturing an Ra volume. In examples, an Ra volume 201 that contains Ra in an acid may be received at a chromatography column 202. In examples, the concentration of Ra volume 201 may be about 5 M HNOs. In examples, Ra volume 201 may be such as volume V3 from FIG.1. Chromatography column 202 may have a body defining an interior chamber that contains an extraction chromatography resin. In some examples, the extraction chromatography resin is MRT™-20 (hereinafter “MRT” or “MRT-20”), available from IBC Advanced Technologies, Inc., 856 East Utah Valley Dr., American Fork, UT, 84003. At the chromatography column 202, the Ra volume 201 is passed through the chromatography column 202 and contacts the resin therein. The Ra from Ra volume 201 is retained within the interior chamber (e.g. is loaded onto the resin). In some examples, the remainder of the Ra volume 201 passes through the chromatography column 202 to form a dilute volume 221 that is removed from the chromatography column 202. In examples, the resin may include one or more other appropriate resins with affinity for Ra.

[0047] In examples, the Ra retained on the resin within the chromatography column 202 is eluted from the resin and is removed from the chromatography column 202 within an Ra outlet volume 203. The wash solution utilized contains a chelating agent. In some examples, the chelating agent may include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTP A), carboxylic acid tetravalent chelators, diphosphonic acid chelators, other appropriate chelators, and / or combinations thereof. In a particular example, the wash solution utilized contains EDTA as a chelating agent. Within chromatography column 202, the chelating agent (e.g. EDTA) chelates the Ra, removing it from the resin and forming a chelated Ra. The Ra outlet volume 203 includes this chelated Ra. The Ra outlet volume 203 may have a concentration of about 0.05 M EDTA. and may have a pH of between about 10-11. Note that herein, the input of the wash / eluent fluid (for example, acid, solvent, or chelating agent) into any columns is not shown in FIG. 2 but the reader will understand that after the loading of a column with whatever material it extracts from a first volume, that extracted material is later removed by the input of the wash / eluent fluid in a separate, distinct step.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0048] In a method of separating and / or concentrating Ra, the Ra outlet volume 203 that contains chelated Ra in acid may be received at a second column 202. Second column 204 may have a body defining an interior chamber that contains a solid or resin. In some examples, the solid is a solid oxidant, such as MnCh (in examples, the MnCh may be in a lone solid state, or may be bound onto a resin substrate / structure). At the second column 204, the Ra outlet volume 203 is passed through the second column 204 and contacts the solid therein. The Ra is therein disassociated from the chelating agent (e.g. from the EDTA) of Ra outlet volume 203, and the Ra is retained within the interior chamber (e.g. is loaded onto the solid). In some examples, the remainder of the Ra outlet volume 203 passes through the chromatography column 202 to form a dilute outlet volume (represented by volume 205) that is removed from the second column 204.

[0049] In some examples, the second column 204 is washed with a first wash volume containing a solvent, to remove at least a first amount of chelating agent (e.g. EDTA) as an outlet volume (represented by volume 205). In some examples, the solvent is an aqueous solvent. In some examples, the solvent comprises water.

[0050] In some examples, the second column 204 is washed with a second wash volume containing an acid, to remove at least a second amount of chelating agent (e.g. EDTA) as an outlet volume (represented by volume 205). In some examples, the acid comprises 0.05 M HNO3.

[0051] In examples, the Ra retained on the solid within the second column 204 is eluted from the solid and is removed from the second column 204 within an eluent volume 207. The eluent solution may comprise an acid. In some examples, the eluent solution (and / or eluent volume 207) may comprise an acid at a concentration of 5 M HNO3. In some examples, the eluent solution (and / or eluent volume 207) may comprise an acid at a concentration of 8 M HNCh. In some examples, the eluent solution (and / or eluent volume 207) may comprise an acid at a concentration of between about 1 - 5 M HNOs. In some examples, eluent volume 207 may be provided to an Ra-processing operation 210. In some examples eluent volume may be diluted further with acid (in a particular example, from 8 M HNOs to 5 M HNOs) prior to being provided to the Ra-processing operation 210. In some examples, Ra-processing operation 210 may include an extraction chromatography column for the generation of Ac, such as extraction chromatography column 104 of FIG. 1.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0052] In a method of generating and / or separating Ac, the Ra outlet volume 203 that contains chelated Ra in acid may be held for a predetermined period of time, to allow for the Ra to generate an amount of Ac. This aged outlet volume 203 may then be received at a second column 202. Second column 204 may have a body defining an interior chamber that contains a solid or resin. In some examples, the solid is a solid oxidant, such as MnCh (in examples, the MnCh may be in a lone solid state, or may be bound onto a resin substrate / structure). At the second column 204, the aged Ra outlet volume 203 is passed through the second column 204 and contacts the solid therein. The Ac is therein disassociated from the chelating agent (e.g. from the EDTA) of aged Ra outlet volume 203, and the Ac is retained within the interior chamber (e.g. is loaded onto the solid). In some examples, the remainder of the aged Ra outlet volume 203 passes through the chromatography column 202 to form a dilute outlet volume (represented by volume 205) that is removed from the second column 204.

[0053] In some examples, the second column 204 is washed with a first wash volume containing a solvent, to remove at least a first amount of chelating agent (e g. EDTA) as an outlet volume (represented by volume 205). In some examples, the solvent is an aqueous solvent. In some examples, the solvent comprises water.

[0054] In some examples, the second column 204 is washed with a second wash volume containing an acid, to remove at least a second amount of chelating agent (e.g. EDTA) as an outlet volume (represented by volume 205). In some examples, the acid comprises 0.05 M HNOs.

[0055] In examples, the Ac retained on the solid within the second column 204 is eluted from the solid and is removed from the second column 204 within an eluent volume 209. The eluent solution may comprise an acid. In some examples, the eluent solution (and / or eluent volume 209) may comprise an acid at a concentration of 0.2 M HNO3. In some examples, the eluent solution (and / or eluent volume 209) may comprise an acid at another concentration of HNO3.

[0056] In some examples, eluent volume 209 may be received at an extraction chromatography column 206. In some examples, eluent volume 209 may be diluted (for example via the addition of an acid volume 211) to reduce the Ac concentration for a diluted eluent volume 213 before being provided to extraction chromatography column 206. In a particular example, the eluent volume 209 at a concentration of Ac 0.2 M HNO3 may be diluted to a diluted eluent volume 213 at a concentration of AcP100172-WO-SEC1-25TPI / 19879.0015WOU10.05 M HNO3. Extraction chromatography column 206 may have a body defining an interior chamber that contains a solid or resin. In some examples, the resin is an LN resin (for example, which may be obtained from Eichrom Technologies, Inc., 1955 University Lane, Lisle, IL, 60532). At the extraction chromatography column 206, the eluent volume 209, 213 is passed through the extraction chromatography column 206 and contacts the resin therein. The Ac is retained within the interior chamber (e.g. is loaded onto the resin). In some examples, the remainder of the eluent volume 209, 213 passes through the extraction chromatography column 206 to form a column outlet volume (represented by volume 215) that is removed from the extraction chromatography column 206, and that may include residual Ra, acid (for example, 0.05 M HNO3), and / or Mn2+ions).

[0057] In examples, the Ac retained on the solid within the extraction chromatography column 206 is eluted from the resin and is removed from the extraction chromatography column 206 within an Ac eluent volume 217. The eluent solution may comprise an acid. In some examples, the eluent solution (and / or eluent volume 217) may comprise an acid at a concentration of 0.05 M HNO3. In some examples, the eluent solution (and / or eluent volume 217) may comprise an acid at another concentration of HNO3.

[0058] In examples, the eluent volume 217 may be passed through a prefilter 208. At or prior to entering prefilter 208, the eluent volume may be diluted, for example, by the addition of acid (in a particular example, by the addition of an acid volume 223 at 0.1 M HNOs). An outlet volume 219 of prefilter 208 comprises the Ac in an acid. In a particular example, the outlet volume 219 comprises Ac at a concentration of 0.1 M HNO3.

[0059] In such Ra separation and Ac generation processes as described with regards to FIG. 2, Mn2+ions may be introduced into the Ra and / or Ac volumes from this process. While it is not known whether the presence of Mn2+is detrimental to downstream radiolabeling of Ac, Mn2+may be removed from the final Ac volumes by polishing steps such as those described in FIG. 1 and / or other chromatography operations such as the use of LN resin as associated with extraction chromatography column 206.

[0060] FIG. 3 illustrates an example method 300 and example operational diagrams for capturing Ra (for example. Ra-225) from an initial volume. In examples, theP100172-WO-SEC1-25TPI / 19879.0015WOU1example system shown may represent a portion of a system such as systems 100 and / or 200.

[0061] At a first loading operation 310, a starting composition 301 volume is loaded (for example, passed through) into a first column 302 (for example, an extraction chromatography column such as chromatography column 202), where composition 301 contacts a resin held within the polishing column 302. The starting composition 301 may include Ra. The starting composition 301 may be such as Ra volume 201. The starting composition 301 may be the product of another upstream operation, for example, a chromatography operation such as extraction chromatography column 104. In examples, the starting composition 301 includes an acid, for example, H2O2, HNO3, HC1, NaNCh, HO A, and / or NaOA, or others. In some examples, the starting composition 301 includes HNO . The concentration of the starting composition 301 may be about Ra 5 M HNOs. In some examples, the concentration of the starting composition 301 may be between about Ra 0.2 M HNO3 and about Ra 8 M HNO3. In some examples, the concentration of the starting composition 301 may be between about Ac Ra M HNO3 and about Ra 8 M HNO3. In some examples, the concentration of the starting composition 301 may be between about Ra 1 M HNOs and about Ra 8 M HNO3. In some examples, the concentration of the starting composition 301 may be between about Ra 1 M HNO3 and about Ra 5 M HNO3. In some examples, the concentration of the starting composition 301 may be between about Ra 4 M HNO3 and about Ra 6 M HNO3. In some examples, the concentration of the starting composition 301 may be less than about Ra 9 M HNOs. In some examples, the concentration of the starting composition 301 may be less than about Ra 6 M HNO3. In some examples, the concentration of the starting composition 301 is measured as concentration of the acid in water and / or another aqueous solvent.

[0062] At the first column 302, which contains a selected extraction chromatography resin such as MRT-20, Ra bound onto the resin. Other components of the stream 301 may pass through the polishing column 302 and form an outlet stream; this outlet stream may include acid (for example HNO3) and other constituents of the starting composition 301 that are not bound to the extraction chromatography resin.

[0063] At a first elution operation 312, a first elution solution 303 volume is passed through the polishing column 302. The first wash solution 303 may be passed through polishing column 302 in a series of elution volumes, sometimes called elution or washP100172-WO-SEC1-25TPI / 19879.0015WOU1fractions (for example. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or more than 13 washes / wash fractions). The elution fractions may occur consecutively. In examples, the first elution solution 303 includes a chelating agent, for example, EDTA. The chelating agent chelates the Ra to release it from the resin and form a chelated Ra, which is eluted out of the first column 302 as outlet volume 305.

[0064] At a second loading operation 314, the outlet volume 305 is provided to a second column 304 (for example, such as second column 204) as a chelated Ra volume 307. Chelated Ra volume 307 is passed through the second column 304. At the second column 304, which contains a selected solid or resin, for example a solid oxidant such as MnCh, Ra is disassociated from the chelating agent (e.g. from the EDTA) and the Ra is bound onto the solid.

[0065] At a first wash operation 316, a first wash solution 311 is provided to the second column 304. The first wash solution 311 may be passed through second column 304 in a series of wash fractions (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or more than 13 washes / wash fractions). The wash fractions may occur consecutively. In examples, the first wash solution 311 includes an solvent, for example, an aqueous solvent. In some examples, the first wash solution 311 includes water.

[0066] At the second column 304, Ra remains bound to the solid, but the conditions created by the first wash solution 311 within the second column 304 cause at least some of the chelating agent to be washed out of the second column 304 in the solvent as outlet volume 313.

[0067] At a second wash operation 318, a second wash solution 315 is passed through the second column 304. In some examples, both first and second wash operations 316, 318 may be performed; in some examples only one or the other of first and second wash operations 316, 318 may be performed. The second wash solution 315 may be passed through second column 304 in a series of wash fractions (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or more than 13 washes / wash fractions). The wash fractions may occur consecutively. In examples, the second wash solution 315 includes an acid, for example, H2O2, HNCh, HC1. NaNCh, HOA, and / or NaOA, or others. In some examples, the second wash solution 315 includes HNCh. The second wash solution 315 may include 0.05 M HNCh. The second wash solution 315 may include 0.2 M HNCh. In some examples, the concentration of the second wash solution 315 may be between about 0.1 M HNCh and about 0.3 M HNCh. In some examples.P100172-WO-SEC1-25TPI / 19879.0015WOU1the concentration of the second wash solution 315 may be between about 0.025 M HNOs and about 0.075 M HNOs. In some examples, the concentration of the second wash solution 315 may be between about 0.01 M HNO3 and about 1.0 M HNO3. In some examples, the concentration of the second wash solution 315 may be between about 0.05 M HNO3 and about 0.5 M HNO3. In some examples, the concentration of the second wash solution 315 may be less than about 1.0 M HNO3. In some examples, the concentration of the second wash solution 315 may be less than about 0.5 M HNO3. In some examples, the concentration of the second wash solution 315 may be less than about 0.05 M HNOs. In some examples, the concentration of the second wash solution 315 is measured as concentration of the acid in water and / or another aqueous solvent.

[0068] At the second column 304. the conditions created by the second wash solution 315 within the second column 304 ensure that the Ra remains bound to the solid. As the second wash solution 315 is passed through the second column 304, at least some remaining chelating agent are washed from the second column 304 in the HNO3 as outlet volume 317. As the second wash solution 315 is passed through the second column 304, in some examples, at least some Ac may be washed out of the second column 304.

[0069] At a second elution operation 320, a second eluent solution 319 is passed through the second column 304. The second eluent solution 319 may be passed through second column 304 in a series of washes / eluent / elution fraction volumes (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or more than 13 fractions). The wash / eluent fractions may occur consecutively. In examples, the second eluent solution 319 includes an acid, for example, H2O2, HNO3, HC1, NaNCh, HOA, and / or NaOA. or others. In some examples, the second eluent solution 319 includes HNO3. The second eluent solution 319 may include about 5 M HNO3. The second eluent solution 319 may include about 8 M HNO3. The second eluent solution 319 may include between about 4 M HNO3 and about 6 M HNO3. The second eluent solution 319 may include between about 7 M HNO3 and about 9 M HNOs. The second eluent solution 319 may include between about 1 M HNO3 and about 10 M HNO3. The second eluent solution 319 may include between about 5 M HNO3 and about 8 M HNO3. In some examples, the concentration of the second eluent solution 319 may be less than about 10 M HNO3. In some examples, the concentration of the second eluent solution 319 may be less than about 9 M HNO3. In some examples, the concentrationP100172-WO-SEC1-25TPI / 19879.0015WOU1of the second eluent solution 319 may be less than about 8 M HNO3. In some examples, the concentration of the second eluent solution 319 may be less than about 6 M HNO3. In some examples, the concentration of the second eluent solution 319 may be less than about 5 M HNO3. In some examples, the concentration of the second eluent solution 319 is measured as concentration of the acid in water and / or another aqueous solvent.

[0070] At the second column 304, the conditions created by the second eluent solution 319 within the second column 304 cause the Ra to be no longer bound to the solid. As the second eluent solution 319 is passed through the second column 304, the Ra is eluted out of the second column 304 in the HNO3 solution (which may include water and / or another aqueous solvent) as Ra eluate / product volume 321.

[0071] In some examples, second elution operation 320 may be repeated one, two, three, or more than three times. In some examples, the second column 304 may be held for a period of time prior to or after any of the iterations of second elution operation 320. In some examples, such a time period may be less than one minute; in some examples, the period of time is less than one hour; in some examples, the prior of time is less than one day; in some examples, the period of time is less than one week; in some examples, the period of time is less than one month. In some examples, the period of time is greater than one minute; in some examples, the period of time is greater than one hour; in some examples, the prior of time is greater than one day; in some examples, the period of time is greater than one week; in some examples, the period of time is less greater than one month. In some examples, the period of time is about 30 minutes. In some examples, the period of time is about 1 hour. In some examples, the period of time is about 2 hours. In some examples, the period of time is about 1 day. In some examples, the period of time is about 2 days. In some examples, the period of time is about 3 days. In some examples, the period of time is about 4 days. In some examples, the period of time is about 5 days. In some examples, the period of time is about 6 days. In some examples, the period of time is about 7 days. In some examples, the period of time is about 2 days. In some examples, the period of time is about 8 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 10 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 11 days. In some examples, the period of time is about 9 days. In some examples, the period of time isP100172-WO-SEC1-25TPI / 19879.0015WOU1about 12 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 13 days. In some examples, the period of time is between about 15 minutes and 1 hour. In some examples, the period of time is between about 2 days and 5 days. In some examples, the period of time is between about 2 days and 15 days. In some examples, the period of time is between about 1 day and 30 days. In some examples, the period of time is between about 10 days and 15 days.

[0072] In some examples, as illustrated in FIG. 3, various outlet volumes 305, 313, 317, and / or 321 of the first column 302 and / or second column 304 may pass through a first selectable valve 306 (of first column 302) or second selectable valve 308 (of second column 304) in fluid connection with an outlet of the associated column.Selectable valves 306, 308 may be able to be placed in one or more positions (for example, 1, 2, 3, 4, or another number of positions). Each example position of selectable valves 306, 308 may route an outlet volume of the associated column to an appropriate storage vessel, disposal means, filtering operation, column, or further processing operation.

[0073] In other examples of the disclosed systems and methods, after Ra has been eluted in as a chelated EDTA stream (for example, after an operation such as operation 312; in a particular example, as 100 mL of Ra 0.05 M EDTA with a pH 10-11), the EDTA may be removed through conversion of the EDTA to its fully protonated form by addition of concentrated HNCL (in a particular example. 100 mL of 15.17 M HNO3). However, EDTA is not soluble in its acidic form and will thus start to precipitate out from the solution. Therefore, neutralization and acid conversion may be performed in a vessel where there is a filter present and the solution can be properly mixed. This may be achieved in a particular example, with acidification being performed in an empty BGB column containing a frit, which is shaken to mix. Then, a peristaltic pump may be utilized to force the solution through the frit, leaving the precipitated EDTA behind. The Ra will remain in solution and will pass through the frit, which can then be used to harvest Ac by passing the Ra / Ac through an extraction chromatography column (in a particular example, a 10 mL BDGA column).

[0074] In some examples, after a second or final elution operation 320, a cationic exchange resin in an additional column may be utilized to separate residual Mn from the Ra. In examples, the Mn may have an affinity for the cation exchange resin. An example of such a resin is Monophos Resin, available from TRISKEM, EichromP100172-WO-SEC1-25TPI / 19879.0015WOU1Technologies LLC, 1955 University Ln., Lisle, IL65532, USA. An acid may be used as the wash fluid for such an operation. Such an operation may be utilized without needing to change the oxidation state of the Mn (for example, from Mn2+to Mn4+).

[0075] FIG. 4 illustrates a method 400 for determining isotope retention at various conditions. For example, method 400 may be utilized to determine retention of an isotope (for example, an isotope of Ra, such as Ra-225) on a selected resin (for example, MnCh or MRT).

[0076] At a preparation operation 416, a resin 404 (for example, an extraction chromatography resin, MnCh, MRT, or other suitable resin) is placed into a container 402. The container may be a vial, flask, test tube, microcentrifuge tube, beaker, or other container of suitable size, shape, and material of construction for its contents and the steps of the method 400.

[0077] At an addition operation 418, a test solution 406 is added to the container 402 that contains the resin 404. The test solution 406 may contain a desired isotope (for example. Ac-225, Ra-225. other isotopes of Ac or Ra, or isotopes of other elements). The test solution 406 may also contain a solvent and / or acid and / or base, and may be aqueous or non-aqueous. The test solution 406 for a particular experimental run of method 400 may have a particular characteristic to be studied. For example, the test solution 406 may have a particular concentration, pH. salt content (for example, potassium, sodium, sodium nitrate, sodium chloride or other salts that may be added to the system or may be present in the system as a contaminant), radioactivity level, temperature, or other characteristic. By performing multiple experimental runs of method 400 with test solutions 406 of variations on one or more characteristics, the effect of the characteristics on the retention of the isotope on the resin 404 may be studied.

[0078] At a contact operation 420, within the container 402, the test solution 406 (including the isotope of the test solution) contacts the resin 404. In examples, at least some of the isotope of the test solution 406 binds to the resin 404, thus creating a bound resin 408 and a second solution 410, the second solution 410 containing less of the isotope than the original test solution 406.

[0079] At a separation operation 422, the second solution 410 is separated, within the container 402, from the bound resin 408. This separation may be performed byP100172-WO-SEC1-25TPI / 19879.0015WOU1centrifugation, settling, vibration, or another appropriate separation technique (in the particular example illustrated in FIG. 4, a centrifuge is shown for illustration purposes).

[0080] In some examples, the container 402 and its contents are left for a period of time after the separation operation 422. In some examples, the period of time is less than one minute; in some examples, the period of time is less than one hour; in some examples, the prior of time is less than one day; in some examples, the period of time is less than one week; in some examples, the period of time is less than one month. In some examples, the period of time is greater than one minute; in some examples, the period of time is greater than one hour; in some examples, the prior of time is greater than one day; in some examples, the period of time is greater than one week; in some examples, the period of time is less greater than one month. In some examples, the period of time is about 30 minutes. In some examples, the period of time is about 1 hour. In some examples, the period of time is about 2 hours. In some examples, the period of time is about 1 day. In some examples, the period of time is about 2 days. In some examples, the period of time is about 3 days. In some examples, the period of time is about 4 days. In some examples, the period of time is about 5 days. In some examples, the period of time is about 6 days. In some examples, the period of time is about 7 days. In some examples, the period of time is about 2 days. In some examples, the period of time is about 8 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 10 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 11 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 12 days. In some examples, the period of time is about 9 days. In some examples, the period of time is about 13 days. In some examples, the period of time is between about 15 minutes and 1 hour. In some examples, the period of time is between about 2 days and 5 days. In some examples, the period of time is between about 2 days and 15 days. In some examples, the period of time is between about 1 day and 30 days. In some examples, the period of time is between about 10 days and 15 days.

[0081] At a final operation 424 (after the period of time, if applicable), the second solution 410 is separated from the bound resin 408. This may include removing one or both of the second solution 410 and the bound resin 408 from the container 402. In the particular example shown, for illustrative purposes in FIG. 4, second solution 410 has been removed from the container 402 (for example, by pipette, pouring, decanting.P100172-WO-SEC1-25TPI / 19879.0015WOU1filtration, or another suitable removal technique) into a second container 414, and the bound resin 408 remains in the original container 402. After this final operation 424, quantitative and / or qualitative testing may be performed to determine the retention of the isotope on the bound resin 408.

[0082] Method 400 as described herein is performed batchwise. Method 300 as described herein may be performed batchwise, continuous, or semi-continuous. In some examples, batchwise operations may be slightly solid-phase diffusion limited, particularly in containers without a flow-through mechanism (for example, a noncolumn container).

[0083] EXAMPLES

[0084] EXAMPLE 1

[0085] This example demonstrates a novel approach in extraction chromatography of actinides by removal of an organic chelator (in this case EDTA) through resins without digestion or precipitation as well as concentrating Ra-225 into a smaller volume from larger ones. First, radium is captured onto MRT-20 (herein also referred to as MRT) after passing a 1.88 L 5 M HNO3 solution of Ra-225 (or any volume of interest) over a 10 mL manually packed column (in 12 g BGB column 21.4 mm ID with bed length 76 mm) equipped with 1 / 5 Oth ID peristaltic tubing using a peristaltic pump set to 100 rpm (1.67 mL / min).

[0086] 100 mL of 0.05 M EDTA pH 10-11 can be used to elute 95-100% of Ra-225 from the MRT-20 column at 100 rpm.

[0087] FIG. 5 illustrates an elution profile of Ra-225 from MRT using 0.05 M EDTA at a pH of 10-11 collected in single bed volume fractions.

[0088] This 0.05 M EDTA pH 10-11 solution containing Ra-225 was be loaded directly onto a 5 mL MnCh (provided from Eichrom) manually packed column conditioned with water in a 4 g BGB column (12.8 mm ID with 60 mm bed length) equipped with l / 50thID peristaltic tubing using a peristaltic pump set to 25 rpm (0.4-0.5 mL / min). This allows for dissociation of the Ra-225 from EDTA and then EDTA to complex any Mn2+ions present. Any Ra-225 or Ac-225 will retain on the MnCh resin in this condition.

[0089] The column is then washed with 100 mL of water at 60 rpm (1 mL / min) to remove excess EDTA.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0090] The column is then rinsed with 50-100 mL of 0.05 M HNO3 or 0.2 M HNO3 at 60 rpm (1 mL / min). This converts any EDTA on the column to be fully protonated and further removed or retained on the column if in an insoluble form.

[0091] Finally, 100 mL of 5 M HNO3 or 50 mL of 8 M HNO3 can be used to remove at least 99% of Ra-225 from the MnCh column at 60 rpm (1 mL / min).

[0092] FIG. 6 illustrates an elution profde of Ra-225 from MnCh using 5 M and 8 M HNO3 collected in single bed volume fractions.

[0093] This method then provides Ra-225 in 100-130 mL 5-8 M HNO3. This may then be used in Ac-225 production / harvesting processes, for example, by passing the solution over a 10 mL BDGA column. If the solution is in 8 M HNO3, it can be molarity adjusted to 5 M HNO3 with the addition of water in order to load onto the BDGA column. This method provides Ra-225 in a usable form for Ac-225 production, reducing the BDGA loading time from 180 minutes to -15-20 minutes, given the large reduction in loading volume, resulting in decreased labor time, and finally higher Ac-225 yields.

[0094] EXAMPLE 2

[0095] It is of note that in a process such as that of Example 1, Mn2+ions may be introduced into the Ra-225 stream from this process. In this example, use of an LN resin has shown that at least 99% of Mn2+ions can be removed from the solution. This can be achieved by loading Ac-225 (for example, produced by the separated Ra-225) onto a 1 mL LN-packed column in 160 mL 0.05 M HNO3 at 1 mL / min.

[0096] The LN column is then washed with 30 mL 0.05 M HNO3 to remove excess Mn2+. Table 1, below, includes recovery' percentage of Mn ions for various load, wash, and elution fractions.

[0097] Table 1 : Mn content (mg) in LN Fractions for Ac-225 purification Sample ID Mn -355 / 55 (mg) Mn Recovery %199-047 Ln Ac 0.003681969 0.0027% Elute_15.5mL-5M HNO3199-049 Ln Ac 5.96079E-06 0.0000% Elute_15.5mL-5M HNO3P100172-WO-SEC1-25TPI / 19879.0015WOU1199-047 Ln Pre Elute_3mL- 0.00036261 0.0003%5M HXO3199-047 Ln Wash 30mL- 2.990266732 2.2228%0.05M HNO3199-047 Ln Load_238mL- 131.5355973 97.7742%0.05M HNO3Total 134.5299146

[0098] The Ac-225 is then eluted from the LN column in 15 mL 0.1 M HNOs.

[0099] This Ac-225 has been measured by ICP-MS (Inductively Coupled Plasma Mass Spectrometry) to demonstrate Mn2+removal. Further, this Ac-225 has been used in radiolabeling of DOTA (tetraxetan, (CFLCFLNCFLCChH^ to show that it does not affect the radiochemical yield, showing at least 99% RCY (radiochemical yield) after 24 hours by iTLC (Instant Thin Layer Chromatography).

[0100] FIG. 7A illustrates a yield of Ac-225 radiolabeling with DOTA showing greater than 99% incorporation, by Free Ac-225. FIG. 7B illustrates a yield of Ac-225 radiolabeling with DOTA showing greater than 99% incorporation, by DOTA / Ac 3800:1.

[0101] EXAMPLE S

[0102] Using materials and equipment consistent with Examples 1 and 2, a 5 mL column was packed with Mn02 resin and conditioned with water. A 100 mL solution of Ra-225 / Ac in 0.05 M EDTA pH 10-11 was loaded onto the column which was then washed with 20 bed volumes (bed volume may be abbreviated as “BV’?herein) of water.

[0103] Selective elution of Ac-225 was achieved using 3 BVs of 0.2 M HNCL.

[0104] Then, Ra-225 was eluted in 10 BVs of 8 M HNO3. This Ra-225 was utilized to generate Ac-225.

[0105] The Ac-225 was purified using a 1 mL LN column. This Ac-225 was then used for radiolabeling DOTA in 0.2 M NH4OAc pH 5.5-6 in 15 min. at 85 °C.

[0106] The Ra-225 / Ac stream w as retained 100% w ith no breakthrough of either radioisotope during loading on Mn02. The pink color of the effluent indicated w ashing out of an EDTA-Mn41complex which was fully removed with extra water rinsing. Excess Mn2+was found in the Ra-225 / Ac eluates which was quantitatively removedP100172-WO-SEC1-25TPI / 19879.0015WOU1from the Ac-225 stream using the LN resin. Recovery' of Ra-225 from MnCh was found to be 99% while Ac-225 was recovered in 96.7% after decay correction from the whole process described. Incorporation of Ac-225 with DOTA was found to be >99% after 24 hr.

[0107] This method demonstrates the ability' to use MnCh resin for concentration of an aqueous solution of Ra-225 / Ac complexed with EDTA, while keeping everything in solution without needing to perform concentration operations such as evaporation or forming / filtering precipitates.

[0108] EXAMPLE 4

[0109] This Example 4 was performed according to the method outlined regarding FIG. 4 above. Table 2 below describes the percent Ra retained on MnCh at various tested pH values and salt content of the solution. In the example, for each test run, 1 mL of MnCh resin was placed in a microcentrifuge tube. 2mL of a solution containing 5 pCi Ra-225 was then added to the microcentrifuge tube. In the test runs 8 and 9, sodium nitrate salt (in the amount listed in Table 2) was added to the test solution to achieve the desired salt content for testing. The tube was then centrifuged. After appropriate centrifuging, the solution in the microcentrifuge tube was held for a period of time, approximately 3 minutes. After the period of time, the liquid solution was separated from the centrifuge tube (in this example, by pipette, leaving the MnCh behind). Gamma results illustrated the amount of Ra retained on the MnCh.

[0110] Table 2: Ra retention by pH and salt content.Run Condition % Ra Retained1 pH 3 99.82 pH 4 99.83 pH 5 99.84 pH 6 99.85 pH 7 99.86 pH 9 99.67 pH 12 98.68 400mg salt 99.29 800mg salt 98.9

[0111] EXAMPLE SP100172-WO-SEC1-25TPI / 19879.0015WOU1

[0112] In this example, 5 mL of MnO2 was prepared in a column. The column was loaded with 30 mL of a neutralized solution containing about 450 pCi Ra-225. A period of time after loading the column (about 8 days), a first elution was performed. This elution utilized 27 BVs of an 0.2 M HNOs solution, followed by 9 BVs of a 0.05 M HNOs solution.

[0113] FIG. 8 illustrates percent recovery of Ra and Ac from MnCh in in bed volumes (BVs) of a first elution. It was observed that at the primary species recovered was Ac.

[0114] EXAMPLE 6

[0115] A period of time (about 12 days) after the first elution of Example 5, a second elution was performed. This elution utilized 18 BVs of an 0.2 M HNO3 solution, followed by 9 BVs of a 5 M HNO solution, finally followed by 9 BVs of an 8 M HNO3 solution. FIG. 9 illustrates percent recovery of Ra from MnCh in bed volumes (BVs) of a second elution. It was observed that at 5M HNO3, a much larger percentage of Ra was recovered than Ac.

[0116] EXAMPLE ?

[0117] In this example, a 5mL MnCh bed was utilized. The MnCh in a column was first loaded with the Ra-containing stream, and then a water wash step was performed. An Ac elution step was performed using 0.1 M HNO3. Then, two Ra elution steps were performed, each using 8 M HNO3. The system was held for a period of time (about 2 days) between the two Ra elution steps. Conditions, volumes, bed volumes, and amounts of Ac and Ra measured for each step are illustrated in Table 3 below. FIG. 10 illustrates example Ra yield from each fraction / step.

[0118] Table 3: Conditions, volumes, and results for Example 7 on 5mL MnCh.Date Measured 4 / 18 / 2025 4 / 18 / 2025 4 / 18 / 2025 4 / 18 / 2025 4 / 18 / 2025 4 / 20 / 20250.1 M AcFraction Initial Load Wash elute RaEl Ra E2 Volume 100 100 100 100 50 50 Total VolumeEluted 0 100 200 300 250 300 BV 0 20 20 20 10 10P100172-WO-SEC1-25TPI / 19879.0015WOU1Ac-225measured 2.643 0.3455 0.02762 2.185 0.05167 0.01788 DF 2 2 2 2 2 2 Ac-225 infraction 528.6 69.1 5.524 437 5.167 0.03576 Ac-225 total 528.6 69.1 74.624 511.624 79.791 79.82676 Ac-225 % 1 0.130723 0.01045 0.826712 0.009775 6.77E-05 Ra-225measured 0.3296 0 0 0.1146 0.3778 0.03215 Ra-225 infraction 176.0064 0 0 61.55994 101.6725 9.466364 Ra-225 total 176.0064 0 0 61.55994 163.2325 172.6988 Ra-225 % 1 0 0 0.34976 0.927423 0.981208

[0119] EXAMPLE S

[0120] In this example, a 5mL MRT bed was utilized. In two loading steps, the MRT in a column was loaded with the Ra-containing stream, and then a water wash step was performed. Then, an Ra elution step was performed, using HNO3. Conditions, volumes, bed volumes, and amounts of Ac and Ra measured for each step are illustrated in Table 4 below. FIG. 11 illustrates example Ra yield from each fraction / step.

[0121] Table 4: Conditions, volumes, and results for Example 8 on 5mL MRT.Initial Ra-225date 4 / 18 / 2025 4 / 18 / 2025 4 / 20 / 2025dT 3.473414 3.430938 1.497153Initial Ra-225(uCi) 52.37674 86.67659 8.829622Date Measured 4 / 21 / 2025 4 / 22 / 2025 4 / 22 / 2025 4 / 22 / 2025WaterFraction Load 1 Load 2 wash Ra eluteVolume 100 160 50 100P100172-WO-SEC1-25TPI / 19879.0015WOU1Total VolumeEluted 100 260 310 410BV 20 20 10 20Ac-225measured 1.548 0.0798 0.08261 0.2247DF 2 2 2 2Ac-225 infraction 309.6 25.536 8.261 44.94Ac-225 total 309.6 25.536 33.797 78.737Ac-225 % 0.872113 0.376246 0.121717 0.662144Ra-225measured 0 0 0 0.2679Ra-225 infraction 0 0 0 149.3618Ra-225 total 0 0 0 149.3618Ra-225 % 0 0 0 1.01

[0122] EXAMPLE 9

[0123] In this example, a 5mL MnCh bed was utilized. The MnCh in a column was first loaded with the Ra-containing stream, and then a w ater w ash step was performed. An Ac elution step was performed using 0.1 M HNO?. Then, three Ra elution steps were performed, each using 8 M HNO3. The system was held for a period of time (about 4 days) between the Ra elution steps. Conditions, volumes, bed volumes, and amounts of Ac and Ra measured for each step are illustrated in Table 5 below . FIG. 12 illustrates example Ra yield from each fraction / step.

[0124] Table 5: Conditions, volumes, and results for Example 9 on 5mL MnCh. Initial Ra- 225 date 4 / 22 / 2025dT 0.081469907Initial Ra- 225 (uCi) 148.7968955P100172-WO-SEC1-25TPI / 19879.0015WOU1DateMeasured 4 / 22 / 2025 4 / 22 / 2025 4 / 23 / 2025 4 / 25 / 2025 4 / 24 / 2025 4 / 28 / 2025RaSM RaS M RaSM 0.1 M Ac 11X03 HNO3 HNO3 Fraction Load Wash elute El E2 E3 Volume 100 100 100 75 75 100 TotalVolumeEluted 100 200 300 375 450 550 BV 20 20 10 15 15 20 Ac-225measured 0.00027 3.91E-05 0.164 0.0682 0.007352 0.002496 DF 2 2 2 2 2 2 Ac-225 infraction 0.054 0.007822 32.8 10.23 1.1028 0.4992 Ac-225 total 0.054 0.007822 32.80782 43.03782 44.14062 44.63982 Ac-225 % 0.000152113 0.000115 0.483274 0.150728 0.024539 0.011108 Ra-225measured 0 0 0.144 0.506 0.01666 0.002824 Ra-225 infraction 0 0 30.21039 86.73164 7.334673 2.01136 Ra-225 total 0 0 30.21039 116.942 124.2767 126.2881 Ra-225 % 0 0 0.203031 0.785917 0.83521 0.848728

[0125] EXAMPLE 10

[0126] In this example, the 5mL MRT bed was utilized. In two loading steps, the MRT in a column was loaded with the Ra-containing stream, and then a water wash step was performed. Then, an Ra elution step was performed, using HNOs.Conditions, volumes, bed volumes, and amounts of Ac and Ra measured for each step are illustrated in Table 6 below.

[0127] Table 6: Conditions, volumes, and results for Example 10 on 5mL MRT.P100172-WO-SEC1-25TPI / 19879.0015WOU1Date Measured 4 / 24 / 2025 4 / 25 / 2025 4 / 25 / 2025 4 / 25 / 2025Fraction Load 3 Load 4 Wash 2 Ra E2Volume 100 240 100 100Total VolumeEluted 100 340 440 540BV 20 20 10 20Ac-225measured 0.221 0.04563DF 2 2 2 2Ac-225 infraction 44.2 0 0 9.126Ac-225 total 44.2 0 0 9.126Ac-225 % 0.978183 0 0 0.201966Ra-225measured 0 0 0 0.1863Ra-225 infraction 0 0 0 99.4842Ra-225 total 0 0 0 99.4842Ra-225 % 0 0 0 0.986539

[0128] EXAMPLE 11

[0129] In this example, a 5mL MnCh bed was utilized. The MnCh in a column was first loaded with the Ra-containing stream, and then a water wash step was performed. An Ac elution step was performed using 0.1 M HNO3. Then, two Ra elution steps were performed, each using 8 M I NO3. The system was held for a period of time (about 3 days) between the Ra elution steps. Conditions, volumes, bed volumes, and amounts of Ac and Ra measured for each step are illustrated in Table 7 below.

[0130] Table 7: Conditions, volumes, and results for Example 11 on 5mL MnCh. Initial Ra-225date 4 / 25 / 2025dT 0.042442P100172-WO-SEC1-25TPI / 19879.0015WOU1Initial Ra-225(uG) 99.28801Date Measured 4 / 25 / 2025 4 / 25 / 2025 4 / 28 / 2025 4 / 28 / 2025 5 / 1 / 20250.1 M Ac Ra8 M Ra8M Fraction Load Wash elute HNO3 El HNO3 E2 Volume 100 100 100 100 50 Total VolumeEluted 100 200 300 400 450 BV 20 20 10 15 15 Ac-225measured 0 0 0.1128 0.008655 0.0122 DF 2 2 2 2 2 Ac-225 infraction 0 0 22.56 1.731 1.22 Ac-225 total 0 0 22.56 24.291 25.511 Ac-225 % 0 0 0.910412 0.069855 0.049233 Ra-225measured 0 0 0.05177 0.1187 0.0397 Ra-225 infraction 0 0 31.67067 72.75914 5.247231 Ra-225 total 0 0 31.67067 104.4298 109.677 Ra-225 % 0 0 0.318978 1.051787 1.104635

[0131] While particular uses of the technology have been illustrated and discussed above, the disclosed technology can be used with a variety of data structures and processes in accordance with many examples of the technology7. The above discussion is not meant to suggest that the disclosed technology7is only suitable for implementation with the data structures, systems, and methods shown and described above.

[0132] This disclosure described some aspects of the present technology with reference to the accompanying drawings, in which only7some of the possible aspects were shown. Other aspects can, however, be embodied in many different forms and should not be construed as limited to the aspects set forth herein. Rather, these aspectsP100172-WO-SEC1-25TPI / 19879.0015WOU1were provided so that this disclosure was thorough and complete and fully conveyed the scope of the possible aspects to those skilled in the art.

[0133] As should be appreciated, the various aspects (e.g., operations, memory arrangements, etc.) described with respect to the figures herein are not intended to limit the technology to the particular aspects described. Accordingly, additional configurations can be used to practice the technology herein and / or some aspects described can be excluded without departing from the methods and systems disclosed herein.

[0134] Similarly, where operations of a process are disclosed, those operations are described for purposes of illustrating the present technology and are not intended to limit the disclosure to a particular sequence of operations. For example, the operations can be performed in differing order, two or more operations can be performed concurrently, additional operations can be performed, and disclosed operations can be excluded without departing from the present disclosure. Further, each operation can be accomplished via one or more sub-operations. The disclosed processes can be repeated.

[0135] Although specific aspects were described herein, the scope of the technology is not limited to those specific aspects. One skilled in the art will recognize other aspects or improvements that are within the scope of the present technology. Therefore, the specific structure, acts, or operations are disclosed only as illustrative aspects. The scope of the technology is defined by the following claims and any equivalents therein. Examples of the disclosure may be described according to the following aspects.

[0136] Aspect 1. A method for separating Ra from a liquid volume, the method comprising: providing the liquid volume, the liquid volume containing Ra and a first concentration of a first acid; contacting the liquid volume with a chromatography resin to obtain an Ra-bound resin; contacting a first eluent volume with the Ra-bound resin, the first eluent volume containing a chelating agent, thereby releasing a first amount of the Ra from the Ra-bound resin and chelating the first amount of the Ra with the chelating agent, to obtain a first output volume including chelated Ra; contacting the first output volume including the first amount of chelated Ra with a solid oxidant to obtain an Ra-bound solid; contacting a first wash volume with the Ra-bound solid, the first wash volume containing a solvent, thereby removing a first amount of the chelating agent to form a second output volume including the solvent and the firstP100172-WO-SEC1-25TPI / 19879.0015WOU1amount of the chelating agent; contacting a second wash volume with the Ra-bound solid, the second wash volume containing a second concentration of a second acid, thereby removing a second amount of the chelating agent to form a third output volume including the second acid and the second amount of the chelating agent; and contacting a second eluent volume with the Ra-bound solid, the second eluent volume containing a third concentration of a third acid, thereby releasing a second amount of the Ra from the Ra-bound solid to obtain an eluent volume including the third acid and the second amount of Ra.

[0137] Aspect 2. The method of aspect 1, wherein the chromatography resin is MRT-20.

[0138] Aspect 3. The method of any of aspects 1-2, wherein the solid oxidant is MnO?.

[0139] Aspect 4. The method of any of aspects 1-3, wherein the Ra is Ra-225.

[0140] Aspect 5. The method of any of aspects 1-4, wherein the solvent comprises water.

[0141] Aspect 6. The method of any of aspects 1-5, wherein the chelating agent comprises EDTA.

[0142] Aspect 7. The method of any of aspects 1-6, wherein the first acid, the second acid, and the third acid comprise HNOs.

[0143] Aspect 8. The method of aspect 7, wherein the first concentration of the first acid is about 5 M HNCh.

[0144] Aspect 9. The method of aspect 7, wherein the second concentration of the second acid is about 0.05 M HNO3.

[0145] Aspect 10. The method of aspect 7, wherein the second concentration of the second acid is about 0.1 M HNO3.

[0146] Aspect 11. The method of aspect 7, wherein the second concentration of the second acid is about 0.2 M HNO3.

[0147] Aspect 12. The method of aspect 7, wherein the third concentration of the third acid is about 5 M HNO3.

[0148] Aspect 13. The method of aspect 7, wherein the third concentration of the third acid is about 8 M HNO3.

[0149] Aspect 14. The method of any of aspects 1-13, wherein the first eluent volume comprises a plurality of eluent volume fractions.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0150] Aspect 15. The method of any of aspects 1-14, wherein the second eluent volume comprises a plurality of eluent volume fractions.

[0151] Aspect 16. The method of any of aspects 1-15, wherein the first wash volume comprises a plurality of eluent volume fractions.

[0152] Aspect 17. The method of any of aspects 1-16, wherein the second wash volume comprises a plurality’ of eluent volume fractions.

[0153] Aspect 18. The method of any of aspects 1-17, further comprising providing the eluent volume to a feed volume of a column containing BDGA.

[0154] Aspect 19. The method of any of aspects 1-18, wherein the eluent volume comprises the third acid, the second amount of Ra, and an amount of Mn, to a feed volume of a column containing a cation exchange resin, thereby separating the Mn from the Ra.

[0155] Aspect 20. The method of any of aspects 1-19, further comprising repeating the operation comprising contacting a second eluent volume with the Ra-bound solid.

[0156] Aspect 21. The method of aspect 20, further comprising holding the Ra-bound solid for a period of time prior to repeating the operation comprising contacting a second eluent volume with the Ra-bound solid.

[0157] Aspect 22. The method of aspect 21, wherein the period of time is greater than about 1 day.

[0158] Aspect 23. A method for generating Ac from a liquid volume, the method comprising: providing the liquid volume, the liquid volume containing Ra and a first concentration of a first acid; contacting the liquid volume with a chromatography resin to obtain an Ra-bound resin; contacting a first eluent volume with the Ra-bound resin, the first eluent volume containing a chelating agent, thereby releasing a first amount of the Ra from the Ra-bound resin and chelating the first amount of the Ra with the chelating agent, to obtain a first output volume including chelated Ra; holding the first output volume for a period of time, thereby allowing the chelated Ra to generate chelated Ac, and forming an aged output volume including the chelated Ac; contacting the aged output volume including the chelated Ac with a solid oxidant to obtain an Ac-bound solid; contacting a first wash volume with the Ac-bound solid, the first wash volume containing a solvent, thereby removing a first amount of the chelating agent to form a second output volume including the solvent and the first amount of the chelating agent; contacting a second wash volume with the Ac-bound solid, the second washP100172-WO-SEC1-25TPI / 19879.0015WOU1volume containing a second concentration of a second acid, thereby removing a second amount of the chelating agent to form a third output volume including the second acid and the second amount of the chelating agent; and contacting a second eluent volume with the Ac-bound solid, the second eluent volume containing a third concentration of a third acid, thereby releasing a second amount of the Ac from the Ac-bound solid to obtain an eluent volume including the third acid and the second amount of Ac.

[0159] Aspect 24. The method of aspect 23, wherein the chromatography resin is MRT-20.

[0160] Aspect 25. The method of any of aspects 23-24, wherein the solid oxidant is MnCh.

[0161] Aspect 26. The method of any of aspects 23-25, wherein the Ra is Ra-225.

[0162] Aspect 27. The method of any of aspects 23-26, wherein the Ac is Ra-225.

[0163] Aspect 28. The method of any of aspects 23-27, wherein the solvent comprises water.

[0164] Aspect 29. The method of any of aspects 23-28, wherein the chelating agent comprises EDTA.

[0165] Aspect 30. The method of any of aspects 23-29, wherein the first acid, the second acid, and the third acid comprise HNO3.

[0166] Aspect 31. The method of aspect 30, wherein the first concentration of the first acid is about 5 M HNO3.

[0167] Aspect 32. The method of aspect 30, wherein the second concentration of the second acid is about 0.05 M HNO3.

[0168] Aspect 33. The method of aspect 30, wherein the second concentration of the second acid is about 0.1 M HNO3.

[0169] Aspect 34. The method of aspect 30, wherein the second concentration of the second acid is about 0.2 M HNO3.

[0170] Aspect 35. The method of aspect 30, wherein the third concentration of the third acid is about 5 M HNO3.

[0171] Aspect 36. The method of aspect 30, wherein the third concentration of the third acid is about 8 M HNO3.

[0172] Aspect 37. The method of any of aspects 23-36, wherein the first eluent volume comprises a plurality' of eluent volume fractions.P100172-WO-SEC1-25TPI / 19879.0015WOU1

[0173] Aspect 38. The method of any of aspects 23-37, wherein the second eluent volume comprises a plurality of eluent volume fractions.

[0174] Aspect 39. The method of any of aspects 23-38, wherein the first wash volume comprises a plurality of eluent volume fractions.

[0175] Aspect 40. The method of any of aspects 23-39, further comprising: providing the eluent volume to a column containing an LN resin; contacting the eluent volume with the LN resin to form: an Ac-bound resin; and a column outlet volume including Mn2+ions, residual Ra, and the third acid; and contacting a third eluent volume with the Ac-bound resin, the third eluent volume containing a fourth concentration of a fourth acid, thereby releasing a third amount of the Ac from the Ac-bound resin to obtain a second eluent volume including the fourth acid and the third amount of Ac.

[0176] Aspect 41. The method of aspect 40, wherein the fourth acid comprises HNO3, and wherein the fourth concentration of the fourth acid is about 0.05 M HNO3.

[0177] Aspect 42. The method of any of aspects 40-41, further comprising providing the second eluent volume to a prefilter to obtain a filter outlet volume, the filter outlet volume including Ac and the acid at a fifth concentration of the fourth acid.

[0178] Aspect 43. The method of aspect 42, wherein the fifth concentration of the fourth acid is about 0.1 M HNO3.

Claims

P100172-WO-SEC1-25TPI / 19879.0015WOU1Claims:

1. A method for separating Ra from a liquid volume, the method comprising: providing the liquid volume, the liquid volume containing Ra and a first concentration of a first acid;contacting the liquid volume with a chromatography resin to obtain an Ra-bound resin;contacting a first eluent volume with the Ra-bound resin, the first eluent volume containing a chelating agent, thereby releasing a first amount of the Ra from the Ra-bound resin and chelating the first amount of the Ra with the chelating agent, to obtain a first output volume including chelated Ra;contacting the first output volume including the first amount of chelated Ra with a solid oxidant to obtain an Ra-bound solid;contacting a first wash volume with the Ra-bound solid, the first wash volume containing a solvent, thereby removing a first amount of the chelating agent to form a second output volume including the solvent and the first amount of the chelating agent;contacting a second wash volume with the Ra-bound solid, the second wash volume containing a second concentration of a second acid, thereby removing a second amount of the chelating agent to form a third output volume including the second acid and the second amount of the chelating agent; andcontacting a second eluent volume with the Ra-bound solid, the second eluent volume containing a third concentration of a third acid, thereby releasing a second amount of the Ra from the Ra-bound solid to obtain an eluent volume including the third acid and the second amount of Ra.

2. The method of claim 1, wherein the chromatography resin is MRT-20.

3. The method of any of claims 1-2, wherein the solid oxidant is MnCh.

4. The method of any of claims 1-3, wherein the Ra is Ra-225.

5. The method of any of claims 1-4, wherein the solvent comprises water.P100172-WO-SEC1-25TPI / 19879.0015WOU16. The method of any of claims 1-5, wherein the chelating agent comprises EDTA.

7. The method of any of claims 1-6, wherein the first acid, the second acid, and the third acid comprise HNOs.

8. The method of claim 7, wherein the first concentration of the first acid is about 5 M HNOs.

9. The method of claim 7, wherein the second concentration of the second acid is about 0.05 M HNOs.

10. The method of claim 7, wherein the second concentration of the second acid is about 0.1 M HNOs.

11. The method of claim 7, wherein the second concentration of the second acid is about 0.2 M HNOs.

12. The method of claim 7, wherein the third concentration of the third acid is about 5 M HNOs.

13. The method of claim 7, wherein the third concentration of the third acid is about 8 M HNOs.

14. The method of any of claims 1-13. wherein the first eluent volume comprises a plurality of eluent volume fractions.

15. The method of any of claims 1-14, wherein the second eluent volume comprises a plurality of eluent volume fractions.

16. The method of any of claims 1-15, wherein the first wash volume comprises a plurality of eluent volume fractions.P100172-WO-SEC1-25TPI / 19879.0015WOU117. The method of any of claims 1-16, wherein the second wash volume comprises a plurality of eluent volume fractions.

18. The method of any of claims 1-17, further comprising providing the eluent volume to a feed volume of a column containing BDGA.

19. The method of any of claims 1-18, wherein the eluent volume comprises the third acid, the second amount of Ra, and an amount of Mn, to a feed volume of a column containing a cation exchange resin, thereby separating the Mn from the Ra.

20. The method of any of claims 1-19. further comprising repeating the operation comprising contacting a second eluent volume with the Ra-bound solid.

21. The method of claim 20, further comprising holding the Ra-bound solid for a period of time prior to repeating the operation comprising contacting a second eluent volume with the Ra-bound solid.

22. The method of claim 21, wherein the period of time is greater than about 1 day.

23. A method for generating Ac from a liquid volume, the method comprising: providing the liquid volume, the liquid volume containing Ra and a first concentration of a first acid;contacting the liquid volume with a chromatography resin to obtain an Ra-bound resin;contacting a first eluent volume with the Ra-bound resin, the first eluent volume containing a chelating agent, thereby releasing a first amount of the Ra from the Ra-bound resin and chelating the first amount of the Ra with the chelating agent, to obtain a first output volume including chelated Ra;holding the first output volume for a period of time, thereby allowing the chelated Ra to generate chelated Ac, and forming an aged output volume including the chelated Ac;contacting the aged output volume including the chelated Ac with a solid oxidant to obtain an Ac-bound solid;P100172-WO-SEC1-25TPI / 19879.0015WOU1contacting a first wash volume with the Ac-bound solid, the first wash volume containing a solvent, thereby removing a first amount of the chelating agent to form a second output volume including the solvent and the first amount of the chelating agent;contacting a second wash volume with the Ac-bound solid, the second wash volume containing a second concentration of a second acid, thereby removing a second amount of the chelating agent to form a third output volume including the second acid and the second amount of the chelating agent; andcontacting a second eluent volume with the Ac-bound solid, the second eluent volume containing a third concentration of a third acid, thereby releasing a second amount of the Ac from the Ac-bound solid to obtain an eluent volume including the third acid and the second amount of Ac.

24. The method of claim 23, wherein the chromatography resin is MRT-20.

25. The method of any of claims 23-24, wherein the solid oxidant is MnCh.

26. The method of any of claims 23-25, wherein the Ra is Ra-225.

27. The method of any of claims 23-26, wherein the Ac is Ra-225.

28. The method of any of claims 23-27, wherein the solvent comprises water.

29. The method of any of claims 23-28, wherein the chelating agent comprises EDTA.

30. The method of any of claims 23-29, wherein the first acid, the second acid, and the third acid comprise HNO3.

31. The method of claim 30, wherein the first concentration of the first acid is about 5 M HNOs.

32. The method of claim 30, wherein the second concentration of the second acid is about 0.05 M HNO3.P100172-WO-SEC1-25TPI / 19879.0015WOU133. The method of claim 30. wherein the second concentration of the second acid is about 0.1 M HNO34. The method of claim 30, wherein the second concentration of the second acid is about 0.2 M HNO?.

35. The method of claim 30, wherein the third concentration of the third acid is about 5 M HNO?.

36. The method of claim 30. wherein the third concentration of the third acid is about 8 M HNO?.

37. The method of any of claims 23-36, wherein the first eluent volume comprises a plurality of eluent volume fractions.

38. The method of any of claims 23-37, wherein the second eluent volume comprises a plurality7of eluent volume fractions.

39. The method of any of claims 23-38, wherein the first wash volume comprises a plurality of eluent volume fractions.

40. The method of any of claims 23-39, further comprising:providing the eluent volume to a column containing an LN resin; contacting the eluent volume with the LN resin to form:an Ac-bound resin; anda column outlet volume including Mn2+ions, residual Ra, and the third acid; andcontacting a third eluent volume with the Ac-bound resin, the third eluent volume containing a fourth concentration of a fourth acid, thereby releasing a third amount of the Ac from the Ac-bound resin to obtain a second eluent volume including the fourth acid and the third amount of Ac.P100172-WO-SEC1-25TPI / 19879.0015WOU141. The method of claim 40, wherein the fourth acid comprises HNO3, and wherein the fourth concentration of the fourth acid is about 0.05 M HNO3.

42. The method of any of claims 40-41, further comprising providing the second eluent volume to a prefilter to obtain a filter outlet volume, the filter outlet volume including Ac and the acid at a fifth concentration of the fourth acid.

43. The method of claim 42, wherein the fifth concentration of the acid is about 0.1 M HNO3.

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