PURIFICATION OF ENRICHED ISOTOPES USING A MULTI-STEP ELUTION PROCESS

Description

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No. 63/651,199, filed May 23, 2024, which is incorporated by reference herein in its entirety.

FIELD

Provided herein are methods for isolating an isotope using ion exchange and a multi-step elution process.

BACKGROUND

Radioisotopes such as lutetium-177 (Lu-177) find use in various diagnostic and treatment methods, including for cancer, and are therefore considered medical isotopes. Methods for producing medical isotopes such as Lu-177 involve capturing an isotope, isolating the captured isotope, and irradiating the isolated isotope to produce the desired medical isotope. However, the presence of unwanted impurities such as sodium produce dangerous radioactive isotopes of the impurities during irradiation, causing safety and handling issues. As such, a clear need exists for methods of isolating a desired isotope that remove such impurities prior to irradiation.

SUMMARY

According to a first aspect of the present disclosure, a method of isolating an isotope from a composition comprising the isotope and one or more impurities comprises:

• • a) loading the composition into a cation exchange resin, wherein the isotope and impurities having a positive oxidation state bind to the cation exchange resin;
  • b) passing a dilute acid through the cation exchange resin, thereby eluting impurities having a +1 oxidation state from the cation exchange resin; and
  • c) eluting the isotope from the cation exchange resin by passing a strong acid through the cation exchange resin, thereby obtaining an isotope solution.

A second aspect includes the method of the first aspect, wherein the isotope has an oxidation state of +3 or greater.

A third aspect includes the method of the first aspect or the second aspect, wherein the isotope has an oxidation state of +3.

A fourth aspect includes the method of any of the previous aspects, wherein the isotope is a ytterbium (Yb) isotope or a gadolinium (Gd) isotope.

A fifth aspect includes the method of any of the previous aspects, wherein the isotope is Yb-176, Gd-152, Gd-155, or Gd-160.

A sixth aspect includes the method of any of the previous aspects, wherein the one or more impurities comprise sodium ions, and wherein the sodium ions are eluted from the cation exchange resin in step b).

A seventh aspect includes the method of any of the previous aspects, wherein the dilute acid has a molarity of less than 2M.

An eighth aspect includes the method of any of the previous aspects, wherein the dilute acid has a molarity of 0.2M to 0.8M.

A ninth aspect includes the method of any of the previous aspects, wherein the dilute acid has a molarity of about 0.4M.

A tenth aspect includes the method of any of the previous aspects, wherein the dilute acid is a mineral acid.

An eleventh aspect includes the method of the tenth aspect, wherein the mineral acid is selected from hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, hydrofluoric acid, hydrobromic acid, perchloric acid, and hydroiodic acid.

A twelfth aspect includes the method of any of the previous aspects, wherein the strong acid has a molarity of 4M to 8M.

A thirteenth aspect includes the method of any of the previous aspects, wherein the strong acid has a molarity of about 6M.

A fourteenth aspect includes the method of any of the previous aspects, wherein the strong acid is a mineral acid.

A fifteenth aspect includes the method of the fourteenth aspect, wherein the mineral acid is selected from hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, hydrofluoric acid, hydrobromic acid, perchloric acid, and hydroiodic acid.

A sixteenth aspect includes the method of any of the previous aspects, further comprising precipitating the isotope from the isotope solution or drying and calcinating the isotope solution.

A seventeenth aspect includes the method of any of the previous aspects, wherein the isotope is precipitated from the isotope solution using oxalate or urea.

An eighteenth aspect includes the method of the sixteenth aspect or the seventeenth aspect, further comprising oxidizing the precipitated or calcinated isotope, thereby obtaining the isotope oxide.

A nineteenth aspect includes the method of the eighteenth aspect, wherein the isotope oxide is obtained by heating the precipitated isotope.

A twentieth aspect includes the method of the eighteenth aspect or the nineteenth aspect, further comprising irradiating the isotope oxide.

A twenty first aspect includes the method of the eighteenth aspect or the nineteenth aspect, further comprising reducing the isotope oxide, and subsequently irradiating the reduced isotope.

A twenty second aspect includes the method of the twentieth aspect or the twenty first aspect, wherein the isotope is Yb-176, and wherein the irradiating produces Lu-177.

A twenty third aspect includes the method of the twentieth aspect or the twenty first aspect, wherein the isotope is Gd-152, Gd-155, or Gd-160, wherein irradiating produces Tb-149, Tb-152, Tb-155, and/or Tb-161.

A twenty fourth aspect includes the method of any of the previous aspects, wherein prior to performing step a), the isotope is captured on a collection target.

A twenty fifth aspect includes the method of the twenty fourth aspect, wherein the composition comprising the isotope and the one or more impurities is obtained by dissolving the captured isotope from the collection target using an acid; and/or burning the collection target.

A twenty sixth aspect includes the method of the twenty fourth aspect or the twenty fifth aspect, wherein the collection target comprises a carbon fiber lattice.

A twenty seventh aspect includes the method of the twenty fourth aspect, the twenty fifth aspect, or the twenty sixth aspect, wherein the isotope is captured on the collection target by accelerating ions towards the collection target, applying a magnetic field to the accelerated ions, thereby mass separating the isotope from other ions, and blocking the other ions using a mass-resolving aperture, thereby capturing the isotope on the collection target.

A twenty eighth aspect includes the method of the twenty seventh aspect, wherein the ions are accelerated towards the collection target using an ion beam.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic showing an exemplary system used for the initial production of the desired metal isotope for purification using the methods described herein. The system includes an ion source (102), an extraction electrode (104) configured to extract ions (e.g., Yb ions) from the ion source, a magnetic analyzer (106) configured to spatially mass separate the metal isotopes produced, a mass resolving aperture (108) positioned and sized to block unwanted isotopes and allow passage of desired isotopes (e.g., Yb-176), and a collection target (110) for receiving the desired isotopes. The collection target may be coupled to a voltage source (112), which holds the collection target (e.g., carbon fiber) at a voltage to offset (at least partially) the energy added to the ion beam provided by the extraction electrodes, such that the energy of the ions is reduced to a thermal energy as the ions reach the collection target causing the ions are caused to stick and form as a film at the collection target. However, it should be understood that the collection target (110) may receive and collect ions of the ion beam without using the voltage source (112). The collection target (110) may comprise a carbon material, for example, the collection target (110) may be 95% or greater carbon.

FIG. 2 is a schematic representation of an exemplary method for purifying an isotope from a composition comprising the isotope and one or more impurities. The method comprises loading the composition comprising an isotope and one or more impurities onto a cation exchange resin. The cation exchange resin comprises negatively charged moieties, such that the isotope of interest (red squares) and impurities (green triangles) having a positive oxidation state bind to the resin. The method subsequently comprises passing a dilute acid through the cation exchange resin, which elutes impurities having a +1 oxidation state from the resin, whereas the isotope of interest (e.g. having an oxidation state of greater than +1, such as +3 or greater) remains bound to the resin. The method then comprises passing a strong acid through the cation exchange resin, thereby eluting the isotope of interest, resulting in an isotope solution. The isotope solution may then be subjected to various additional steps (e.g. precipitation, oxidation, reduction, and/or irradiation) to obtain the desired product, e.g. the desired medical isotope.

DEFINITIONS

Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear; in the event, however of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

As utilized herein, the terms “approximately,” “about,” “substantially”, and similar terms are intended to have a broad meaning in harmony with the common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to the precise numerical values or idealized geometric forms provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the disclosure as recited in the appended claims.

The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “and” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not.

For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated.

The terms “isolating” and “purifying”, along with linguistic variations thereof, are used interchangeably herein and refer to the act of obtaining an isotope that is substantially free from impurities. The terms do not necessarily indicate that the one or more impurities are completely absent from the “isolated” or “purified” isotope.

The term “impurity” is used herein in the broadest sense and refers to any moiety other than the isotope of interest (e.g., any moiety other than the isotope to be purified).

Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the present disclosure. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.

DETAILED DESCRIPTION

Radioisotopes, or radionuclides, offer a valuable strategy for cancer diagnostics and therapeutics. Lu-177 is a theranostic radionuclide useful for both diagnostic testing and therapeutic treatments. Specifically, during decay Lu-177 emits a low energy beta particle that is suitable for treating cancer, including neuro endocrine tumors, prostate, breast, renal, pancreatic, and other cancers. Lu-177 also emits two gamma rays that can be used for diagnostic testing. In the coming years, approximately 70,000 patients per year will need no carrier added Lu-177 during their medical treatments.

Methods for producing radioisotopes such as Lu-177 involve irradiation, for example irradiation of Lu-176 or irradiation of Yb-176, which subsequently decays to produce Lu-177. However, the presence of impurities during irradiation can lead to dangerous radioactive isotopes of the impurities being produced. For example, the presence of sodium (typically present in the form of stable Na-23) during irradiation becomes quite problematic, as when irradiated, a portion of the Na-23 becomes Na-24, a radioactive isotope of sodium that emits high level of gammas, which is hard to shield and is difficult for travel and use in hot cells. This creates a safety and handling problem during the subsequent separation process (e.g., the separation of Lu-177 from the Yb-176 after irradiation). As such, methods for isolating a desired isotope prior to irradiation that substantially eliminate impurities and thus significantly reduce this risk are needed. The present disclosure addresses this and other issues by providing a method for isolating an isotope from a composition comprising the isotope and one or more impurities. The method involves ion exchange (e.g. cation exchange) and a multi-step elution process which eliminates impurities prior to eluting the desired isotope from the ion exchange resin.

In some aspects, provided herein are methods of isolating (e.g. purifying) an isotope from a composition comprising the isotope and one or more impurities. In some embodiments, provided herein is a method of isolating an isotope from a composition comprising the isotope and one or more impurities, comprising: loading the composition into a cation exchange resin, such that the isotope and impurities having a positive oxidation state bind to the cation exchange resin; passing a dilute acid through the cation exchange resin, thereby eluting impurities having a +1 oxidation state from the cation exchange resin; and eluting the isotope from the cation exchange resin by passing a strong acid through the cation exchange resin, thereby obtaining an isotope solution.

The methods of the present disclosure may be applied to any target isotope, particularly isotopes useful in the production of medical isotopes, including ytterbium isotopes (Yb-176) and gadolinium (Gd) isotopes, which are the precursor material for the production of certain terbium (Tb) medical isotopes. In particular, in addition to Yb-176, the present disclosure is applicable to the capture and purification of Gd-152, Gd-155, and Gd-160, which may be used to produce Tb-149, Tb-152, Tb-155, and Tb-161.

In some embodiments, the metal isotope (Yb-176) of which isolation (e.g. purification) is desired is initially produced using an ion beam (e.g., a Yb ion beam). In some embodiments, the metal isotope of which isolation is desired by spatially mass separating the metal isotopes of the ion beam using a magnetic field, blocking undesired metal isotopes of the ion beam using a mass resolving aperture, and collecting the desired isotope on a collection target, such as a carbon fiber collection target. One or more steps in this initial production and capture process can result in the presence of the one or more impurities, which are removed using the purification method described herein. The desired isotope may be captured on a collection target by holding the collection target at a voltage that causes a reduction of the extraction energy of the ion beam as it approaches the collection target, allowing the desired isotope to stick on the collection target. However, it should be understood that the collection target may receive and collect ions of the ion beam without being held at a voltage. Once collected on the collection target, the desired isotope is extracted from the collection target and purified using the methods described herein. Exemplary systems and methods for production capture of isotopes (e.g., using an ion beam) are described in U.S. Pat. Appl. Nos. US2022/0363558, US/2023/0109221, and PCT Appl. No. PCT/US2021/045855, the entire contents of each of which are incorporated herein by reference in their entireties.

An exemplary system used for the initial production of the desired metal isotope is shown in FIG. 1. The system includes an ion source (102), an extraction electrode (104) configured to extract ions (e.g., Yb ions) from the ion source, a magnetic analyzer (106) configured to spatially mass separate the metal isotopes produced, a mass resolving aperture (108) positioned and sized to block unwanted isotopes and allow passage of desired isotopes (e.g., Yb-176), and a collection target (110) for receiving the desired isotopes. The collection target may be coupled to a voltage source (112), which holds the collection target (e.g., carbon fiber) at a voltage to offset (at least partially) the energy added to the ion beam provided by the extraction electrodes, such that the energy of the ions is reduced to a thermal energy as the ions reach the collection target causing the ions are caused to stick and form as a film at the collection target. However, it should be understood that the collection target (110) may receive and collect ions of the ion beam without using the voltage source (112).

In some embodiments, the collection target is a carbon fiber lattice. In some embodiments, the carbon fiber lattice includes multiple layers of carbon fiber arranged in different directions. For example, the collection target may comprise rayon felt. The collection target is burnable and the captured isotope may be gathered from the collection target by burning the collection target, leaving behind a residue comprising the isotope. If the enriched isotope is obtained by burning, the residue is then dissolved in an acid, such as nitric acid, to produce a solution comprising the isotope. This solution constitutes the composition comprising the isotope and one or more impurities used in the purification methods described herein. Alternatively, the isotope may be obtained from the collection target by dissolving the isotope from the collection target, e.g. using an acid, resulting in a solution comprising the isotope (i.e., the composition comprising the isotope and one or more impurities).

In some embodiments, the method of isolating an isotope from the composition comprising the isotope and one or more impurities comprises loading the composition comprising the isotope and the one or more impurities into a cation exchange resin. A cation exchange resin typically comprises a polymer material (e.g. a crosslinked polymer, such as crosslinked polystyrene beads) comprising negatively charged moieties such that positively charged molecules and/or ions having a positive oxidation state bind to the negatively charged moieties and are retained within the resin. Generally, the polymer material (e.g. beads) are porous, thereby providing a relatively large surface area to facilitate trapping of ions. Any suitable cation exchange resin may be used. In some embodiments, the cation exchange resin is a strongly acidic cation exchange resin. In some embodiments, the cation exchange resin is a weakly acidic cation exchange resin. A cation exchange resin is typically packed into a suitable container, e.g. an ion exchange column. An ion exchange column packed with a cation exchange resin is also referred to herein as a “cation exchange column”. The cation exchange resin may be packed into the column by any suitable method, including conventional techniques such as slurry packing or dry packing.

In some embodiments, the isotope has an oxidation state of +3 or greater. The terms “oxidation state” and “oxidation number” are used interchangeably herein and refer to the hypothetical charge that an atom would have if all bonds to other atoms were fully ionic. The oxidation state of an isotope may be determined by various methods as known in the art. For example, the oxidation state of an atom may be determined using a Lewis structure, which allows calculation of the oxidation state of an atom by computing the difference between the number of valence electrons that a neutral atom would have and the number of electrons that belong to that atom in a Lewis structure. Alternatively, the oxidation state may also be calculated without a Lewis structure. A given isotope can have more than one possible oxidation state. For example, ytterbium and gadolinium are most often in the +3 oxidation state, although other oxidation states are possible (e.g. ytterbium can also exist in the +2 oxidation state). In some embodiments, the isotope is a lanthanide isotope. In some embodiments, the isotope is a lanthanide isotope having an oxidation state of +3. In some embodiments, isotopes suitable for subsequent production of medical isotopes, such as by irradiation, are desired. For example, the methods described herein are particularly useful for isolation of ytterbium isotopes and/or gadolinium isotopes. In some embodiments, the isotope is an ytterbium isotope. In some embodiments, the isotope is Yb-176. In some embodiments, the isotope is a gadolinium isotope. In some embodiments, the isotope is Gd-152, Gd-155, or Gd-160.

In some embodiments, after loading the composition comprising the isotope and one or more impurities into the cation exchange resin (and subsequent binding of ions having a positive oxidation state to the negatively charged moieties in the resin), the method comprises passing a dilute acid through the cation exchange resin to elute impurities having a +1 oxidation state from the cation exchange resin. As used herein, the term “dilute acid” refers to an acid having a molarity of less than 2M. Use of a dilute acid having a molarity of less than 2M elutes impurities having a +1 oxidation state from the cation exchange resin, whereas ions having a higher oxidation state (e.g. a +3 oxidation state) remain bound to the negatively charged moieties within the resin. In contrast, use of an acid having a strength of greater than 2M would undesirably elute ions having a higher oxidation state (e.g. a +3 oxidation state) from the resin, which could result in loss of the desired isotope.

The dilute acid may be a mineral acid (e.g. a mineral acid having a molarity of less than 2M). For example, the dilute acid may be a mineral acid selected from hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, hydrofluoric acid, hydrobromic acid, perchloric acid, and hydroiodic acid. In some embodiments, the dilute acid has a molarity of less than 2M, less than 1.9M, less than 1.8M, less than 1.7M, less than 1.6M, less than 1.5M, less than 1.4M, less than 1.3M, less than 1.2M, less than 1.1M, less than 1.0M, less than 0.9M, less than 0.8M, less than 0.7M, less than 0.6M, less than 0.5M, less than 0.4M, less than 0.3M, or less than 0.2M.

In some embodiments, the dilute acid has a molarity of about 0.1M to about 2M, about 0.1 to about 1.5M, about 0.1 to about 1M, or about 0.2M to about 0.8M, about 0.3M to about 0.7M, or about 0.4M to about 0.6M. In some embodiments, the dilute acid has a molarity of about 0.1M, about 0.2M, about 0.3M, about 0.4M, about 0.5M, about 0.6M, about 0.7M, about 0.8M, about 0.8M, about 1M, about 1.1M, about 1.2M, about 1.3M, about 1.4M, about 1.5M, about 1.6M, about 1.7M, about 1.8M, or about 1.9M.

In some embodiments, the composition comprises one or more impurities that are removed (e.g. eluted) from the cation exchange resin by passing the dilute acid through the resin. In some embodiments, the one or more impurities result from the method used to produce the isotope of interest, for example from the ion beam and/or from the collection target (e.g. the carbon fiber collection target) used to produce the isotope of interest prior to subsequent purification using the methods described herein. An exemplary impurity described herein is sodium ions (e.g. Na-23), but the methods described herein can be applied to remove any impurity having a suitable oxidation state or any impurity having a suitable charge. In some embodiments, a first round of impurities is removed upon addition of the composition comprising the isotope and the one or more impurities to a cation exchange resin by simply not binding to the negatively charged moieties in the cation exchange resin. In some embodiments, a second round of impurities having a +1 oxidation state (or an appropriate positive charge) are removed by elution using a dilute acid. In some embodiments, still other impurities remain bound to the resin and are not removed upon elution of the isotope of interest using the strong acid.

In some embodiments, the one or more impurities comprise sodium ion (e.g. Na-23). In some embodiments, one or more characteristics of the cation exchange resin (e.g. porosity, bead size, etc.) and/or one or more characteristics of the acid used to elute the impurities (e.g. the specific type of acid, the molarity of the acid) are modulated to maximize removal of sodium (e.g. Na-23) during the step of passing the dilute acid through the cation exchange resin.

In some embodiments, after passing the dilute acid through the cation exchange resin to elute impurities, the method comprises eluting the desired isotope from the cation exchange resin by passing a strong acid through the cation exchange resin. The resulting solution comprising the eluted isotope of interest (e.g. the desired ytterbium isotope, the desired gadolinium isotope) is referred to as an “isotope solution.” The isotope solution or the purified isotope contained therein may be subjected to one or more additional processing steps. For example, the isotope solution or the isotope contained therein can be subjected to precipitation, oxidation, reduction, and/or irradiation steps, depending on the desired use of the isotope.

The term “strong acid” refers to an acid having a molarity of 4M or greater. In some embodiments, the strong acid is a mineral acid. For example, the strong acid may be a mineral acid selected from hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, hydrofluoric acid, hydrobromic acid, perchloric acid, and hydroiodic acid. In some embodiments, the strong acid has a molarity of at least 4M, at least 5M, at least 6M, at least 7M, or at least 8M. In some embodiments, the strong acid has a molarity of about 4M to about 8M. In some embodiments, the strong acid has a molarity of about 4M to about 8M, about 4.1M to about 7.9M, about 4.2M to about 7.8M, about 4.3M to about 7.7M, about 4.4M to about 7.6M, about 4.5M to about 7.5M, about 4.6M to about 7.4M, about 4.7M to about 7.3M, about 4.8M to about 7.2M, about 4.9M to about 7.1M, about 5M to about 7M, about 5.1M to about 6.9M, about 5.2M to about 6.8M, about 5.3M to about 6.7M, about 5.4M to about 6.6M, about 5.5M to about 6.5M, about 5.6M to about 6.4M, about 5.7M to about 6.3M, about 5.8M to about 6.2M, about 5.9M to about 6.1M, or about 6M. Use of a strong acid having a molarity of at least 4M (e.g. 4M to 8M) elutes the desired metal isotope (e.g. the isotope having a +3 oxidation state) from the resin. In contrast, use of an acid having a molarity of less than 4M would fail to elute the desired isotope from the resin.

Elution of the desired isotope from the cation exchange resin (e.g. using the strong acid) produces an isotope solution. In some embodiments, the method further comprises precipitating the isotope from the isotope solution. The isotope may be precipitated using any suitable reagent, including oxalate or urea. In some embodiments, after eluting the desired isotope from cation exchange resin to form the isotope solution, the isotope solution may be dried and calcinated. Drying and calcinating may be done instead of precipitating the isotope. In some embodiments, the method further comprises oxidizing the precipitated or calcinated isotope. For example, in some embodiments the method further comprises heating the precipitated or calcinated isotope, thereby producing an isotope oxide (e.g. Yb-176 oxide). The isotope oxide can then be irradiated to produce a medical isotope, such as Lu-177. Alternatively, the isotope oxide can be first converted to a captured metal via a reduction process, and then irradiated to produce the medical isotope. For example, the captured isotope material may be irradiated in an irradiation facility, such as a nuclear reactor or an accelerator system. During irradiation, some of the captured isotope material undergoes a neutron capture reaction. For example, Yb-176 may undergo a neutron capture reaction to become Yb-177, which decays to Lu-177.

In some embodiments, the methods provided herein achieve greater than 99% purity of the chemical element following purification on an isotopic basis. In some embodiments, the methods provided herein achieve greater than 99.9%, greater than 99.99%, greater than 99.999%, greater than 99.9999%, or greater than 99.99999% purity of the chemical element following purification on an isotopic basis. For example, in some embodiments the methods provided herein achieve purified Yb-176 that is greater than 99% pure on an isotopic basis. This includes Yb-176 that is greater than 99.9%, greater than 99.99%, greater than 99.999%, or greater than 99.9999% pure on an isotopic basis.

The present invention, thus generally described, will be understood more readily by reference to the following examples, which are provided by way of illustration and are not intended to be limiting of the present invention.

EXAMPLES

Example 1

This example demonstrates a multi-step method for purification of a desired isotope. In this example, the desired metal isotope was Yb-176. However, it is understood that any desired metal isotope may be purified using the methods provided herein.

The desired metal isotope (Yb-176) was produced from an ion beam (e.g., a Yb ion beam) by spatially mass separating the metal isotopes of the ion beam using a magnetic field, blocking undesired metal isotopes of the ion beam using a mass resolving aperture, and collecting the desired isotope on a collection target (e.g. a carbon fiber lattice). This process of producing the desired metal isotope and capturing the isotope on a collection target is also referred to herein as isotope “enrichment”. The isotope on the collection target is also referred to herein as an “enriched isotope”.

The collection target used in the enrichment process (e.g., the carbon fiber lattice) often contains some impurities, such as sodium (typically present in the form of stable Na-23). If this sodium remains with the captured isotope material during subsequent irradiation, a portion of the Na-23 becomes Na-24, a radioactive isotope of sodium that emits high level of gammas, which is hard to shield and is difficult for travel and use in hot cells. This creates a safety and handling problem during the subsequent separation process. As such, a method involving ion exchange and multiple elution steps was designed and utilized herein to isolate the desired isotope from impurities, including sodium, leading to a significantly safer and improved method for producing purified metal isotopes for subsequent irradiation.

Prior to performing the ion exchange and elution steps described in more detail below, the enriched isotope was obtained from (e.g. collected from, harvested from, isolated from, etc.) the collection target. The enriched isotope can be obtained from the collection target by burning the collection target, leaving behind a residue comprising the isotope. If the enriched isotope is obtained by burning, the residue is then dissolved in an acid, such as nitric acid, to produce a solution comprising the isotope. This solution is referred to herein as a “captured isotope solution”. Alternatively, target by dissolution of the isotope directly from the collection target, e.g. using an acid, resulting in a solution comprising the isotope (i.e., a captured isotope solution).

The captured isotope solution was then loaded onto an ion exchange column packed with a cation exchange material. Next, a dilute acid (e.g. 0.4 M mineral acid, such as HCl) was passed through the ion exchange column to elute (e.g., remove) ions with a +1 oxidation state, which includes the sodium (e.g., the Na-23) and other +1 impurities. The mineral acid should be sufficiently diluted to prevent removal of higher positive oxidation states, which could remove the target captured isotopes. For example, the dilute mineral acid should by less than 2 M, because at 2 M and above, the mineral acid may remove some of the +3 ions, which include the Yb-176. Next, a strong mineral acid was passed through the ion exchange column to elute the +3 ions, which include the captured isotope (e.g., Yb-176), such that the resultant isotope solution comprises a high purity of the captured isotope (e.g., a high purity of Yb-176). The strong mineral acid (e.g., HCl) may comprise about 6 M, for example, a molarity in a range of 4M-8M.

Next, the captured isotope (e.g., Yb-176) was precipitated from the resultant isotope solution using oxalate or urea, which precipitates the captured isotope as a captured isotope oxalate (e.g., Yb-176 oxalate). The captured isotope oxalate was then heated to convert it to a captured isotope oxide (e.g., Yb-176 oxide). The captured isotope oxide may then be irradiated or first converted to a captured metal via a reduction process and then irradiated. As described above, the methods provided herein achieve a high purity of the desired isotope, without significant levels of dangerous impurities such as sodium, such that the desired isotope is achieved during radiation without hazardous isotopes being produced during the irradiation process. Once irradiated, the captured isotope produces a medical isotope, such as Lu-177.