Gaseous emanation radionuclide generators and methods including environmental control

Abstract

Some aspects are related to systems and methods for generating radionuclides. In some embodiments, the disclosed systems and methods control an environment in which progeny radionuclides emanate from a precursor radionuclide source and / or in which the progeny radionuclides are collected. This may include controlling a temperature and / or humidity of the environment. Some aspects are related to systems and methods including a collection surface, such as an interior surface of a container, with a collection surface area and a precursor radionuclide source with a source surface area. In some embodiments, a ratio of the collection surface area to the source surface area may be selected to be within a predetermined range.

Description

Atty. Dkt. No.: 137664-5012-WOGASEOUS EMANATION RADIONUCLIDE GENERATORS AND METHODS INCLUDING ENVIRONMENTAL CONTROLCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application No.63 / 777,921, filed March 26, 2025, and U.S. Provisional Application No. 63 / 798,288, filed May 1, 2025, each titled “Gaseous Emanation Radionuclide Generators and Methods Including Environmental Control”, each of which is incorporated herein by reference in its entirety.FIELD

[0002] Disclosed embodiments are related to radionuclide generating systems and related methods.BACKGROUND

[0003] Radionuclides such as lead 212 (212Pb) may be used in various applications. For example,212Pb may be used as a therapeutic in radiation treatments for various health conditions, including various cancers. Lead 212 may be formed as a progeny radionuclide in the decay chain of a precursor radionuclide such as thorium, radium, or radon. Containers for capturing and using a desired progeny radionuclide may be exposed to a precursor radionuclide under ambient conditions.SUMMARY

[0004] Some aspects are related to methods.

[0005] In some embodiments, the method is a method of generating radionuclides. In some embodiments, the method comprises controlling an environment present in an interior volume defined by a container; exposing one or more surfaces at least partially defining the interior volume of the container to a precursor radionuclide source comprising a precursor radionuclide; and emanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.1DBl / 167702246.1Atty. Dkt. No.: 137664-5012-WO

[0006] In some embodiments, the method comprises exposing one or more surfaces at least partially defining an interior volume of a container to a precursor radionuclide source comprising a precursor radionuclide, wherein the interior volume includes an interior surface area, the precursor radionuclide source includes a source surface area, and a ratio between the source surface area and the interior surface area is greater than or equal to 1 :25 and less than or equal to 1:280; and emanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

[0007] Some aspects are related to systems.

[0008] In some embodiments, the system is a system for generating radionuclides. In some embodiments, the system comprises a precursor radionuclide source comprising a precursor radionuclide and configured to generate gaseous progeny radionuclides, wherein the precursor radionuclide source is configured to be fluidly coupled to an interior volume of a container; one or more sensors configured to measure one or more parameters of an environment present in the interior volume of the container; an environmental controller configured to control at least one of the one or more parameters of the environment present in the interior volume of the container; and at least one processor configured to receive signals from the one or more sensors and control the environmental controller to maintain the at least one of the one or more parameters within a predetermined operating range.

[0009] In some embodiments, the system comprises a precursor radionuclide source having a source surface area and comprising a precursor radionuclide configured to generate gaseous progeny radionuclides; a container having an opening and one or more surfaces at least partially defining an interior volume that is configured to receive the precursor radionuclide source, wherein the interior volume includes an interior surface area, and wherein a ratio between the source surface area and the interior surface area is greater than or equal to 1 :25 and less than or equal to 1 :280.

[0010] It should be appreciated that the foregoing concepts, and additional concepts discussed below, may be arranged in any suitable combination, as the present disclosure is not limited in this respect. Further, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying figures.DBl / 167702246.1 2Atty. Dkt. No.: 137664-5012-WOBRIEF DESCRIPTION OF DRAWINGS

[0011] The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. In the drawings:

[0012] FIG. 1 is a plot showing the decay chain of a precursor radionuclide, according to some embodiments.

[0013] FIG. 2A is a cutaway view of a radionuclide generator during insertion of a container into the radionuclide generator, according to some embodiments.

[0014] FIG. 2B is a cutaway view of the radionuclide generator of FIG. 2A during exposure of the container to the precursor radionuclide source, according to some embodiments.

[0015] FIG. 2C is a cross sectional view of a precursor radionuclide source holder in an extended configuration, according to some embodiments.

[0016] FIG. 2D is a cross sectional view of a precursor radionuclide source holder in a retracted configuration, according to some embodiments.

[0017] FIG. 3 is a method flow diagram for generating radionuclides, according to some embodiments.

[0018] FIG. 4A is a plot of the average absolute humidity in a collection chamber of a generator and emanation yield of the generator for different trials, according to some embodiments.

[0019] FIG. 4B is a plot of the average temperature in a collection chamber of a generator and emanation yield of the generator for different trials, according to some embodiments.

[0020] FIG. 5A-5B are plots of the average absolute humidity, temperature, and emanation yield for a generator including a precursor radionuclide source as a function of time, according to some embodiments.

[0021] FIGS. 6A-6C are plots of the average emanation yield for a generator including a precursor radionuclide source as a function of time, according to some embodiments.

[0022] FIGS. 7A-7B are images of an experimental setup for measuring temperature and / or humidity within a container, according to some embodiments.DBl / 167702246.1 3Atty. Dkt. No.: 137664-5012-WO

[0023] FIGS. 7C-7G are plots of the relative humidity within a container as a function of time, according to some embodiments.

[0024] FIG. 7H is a plot of the relative humidity as a function of temperature within a container, according to some embodiments.

[0025] FIG. 8 is a plot showing the purity of lead 212 grand-progeny radionuclides from thorium 228 precursor radionuclides, according to some embodiments.

[0026] FIGS. 9A- 9C are graphs illustrating the results from three generators (GEN-A, GEN-B and GEN-C) showing the effect of conditioning on emanation yields.

[0027] FIG. 10 is a graph illustrating the effect of conditioning on emanation yields.

[0028] FIG. 11 is a graph providing an overview of emanation data from twelve high activity (approximately IGBq) GMP precursor radionuclide sources.

[0029] FIGS. 12A- 12D are graphs illustrating relative humidity (RH) and temperature measured inside 30mL collection vials during emanations of a generator over time. The various graphs represent various additions to or treatment of the 30mL collection vial.DETAILED DESCRIPTION

[0030] Radionuclides may be used for a variety of applications in such fields as medicine, biology, physics, and other industries. Some radionuclides which possess relatively short half-lives may be appropriate for use in various medical applications, such as targeted alpha-particle therapy (TAT). Radionuclides possessing relatively short half-lives may be preferable for some applications so they can be administered to a patient to treat a particular condition (e.g., any of various cancers such as prostate or carcinoid cancers) while limiting the patient’s time of exposure to radioactivity. Treatments with radionuclides having shorter halflives may therefore result in fewer and / or less severe side effects than treatments with radionuclides having longer half-lives. In some applications, lead 212 (212Pb) may be a desirable radionuclide for use in TAT or other treatments or applications because it has a half-life of about 10.6 hours.

[0031] Radionuclides having short half-lives may be generated within systems for generating radionuclides (e.g., a radionuclide generator) close to a point of use. For example, a radionuclide generator may include a precursor radionuclide source including precursor radionuclide having a long half-life, and the precursor radionuclide may decay into a progenyDBl / 167702246.1 4Atty. Dkt. No.: 137664-5012-WOradionuclide having a short half-life at or close to the point of use. Such a workflow may include the use of a container that is used in tandem with the radionuclide generator such that the container captures the progeny radionuclide (e.g., lead 212). As a non-limiting example, a radionuclide generator may include a precursor radionuclide source comprising thorium 228, which decays into the gaseous radon 220 that emanates to a container surrounding the source. The gaseous radon 220 may then further decay into lead 212 for use as a therapeutic.

[0032] In some configurations of systems, the yield of progeny radionuclide from the precursor radionuclide source in a radionuclide generator is an important parameter which impacts the utility and lifetime of the generator. Moreover, the yield of progeny radionuclides from the precursor radionuclide source may impact the dosage of therapeutics made using the radionuclide generator, and thus ultimately the efficacy of such therapeutics. Typically, radionuclide generators that utilize precursor radionuclide sources comprising long half-life precursor radionuclides to generate short half-life progeny radionuclides at or close to the point of use have a yield that is below the theoretical maximum yield (i.e., an expected maximum amount of progeny radionuclides that form from a known amount of precursor radionuclides). Furthermore, the yield of progeny radionuclides from the precursor radionuclide source may be inconsistent over time.

[0033] In view of the above, the inventors have recognized that controlling the environmental conditions in which a precursor radionuclides decays and in which progeny radionuclides may be collected may affect the yield and overall efficiency of progeny radionuclides obtained from a radionuclide generator. For instance, controlling various environmental conditions may impact the decay of a precursor radionuclide, emanation of a progeny radionuclide (e.g., a gaseous progeny radionuclide), and the decay and / or deposition of the progeny radionuclide onto a surface such as the interior surface of a container used to collect the one or more progeny radionuclides. More specifically, the inventors have recognized the benefits associated with controlling the humidity within an environment in which the precursor radionuclide of the precursor radionuclide source decays and progeny radionuclides are collected, and that in certain instances, controlling the humidity within the environment affects the yield obtained from the precursor radionuclide source. The inventors have further recognized that controlling the temperature within the environment in which the precursor radionuclide of the precursor radionuclide source decays and progeny radionuclides are collected may also affectDBl / 167702246.1 5Atty. Dkt. No.: 137664-5012-WOthe yield obtained from the precursor radionuclide source. In some embodiments, both the temperature and the humidity during emanation and collection of one or more progeny radionuclides may be modulated and / or controlled to increase the yield obtained from the precursor radionuclide source.

[0034] In the above and other embodiments disclosed herein, it should be understood that the environment in which the precursor radionuclide of the precursor radionuclide source decays and progeny radionuclides therefrom are collected may be an interior volume of a container exposed to the precursor radionuclide source. However, other embodiments in which the environment associated with the emanation and collection of one or more progeny radionuclides include: flow-based generators, generators including collection chambers, and / or other appropriate constructions are contemplated as the disclosure is not limited in this fashion.

[0035] The inventors have further recognized that controlling a ratio between a surface area of a precursor radionuclide source (i.e., a source surface area) and a collection surface, such as an interior surface area of a container configured to be exposed to the emanated progeny radionuclides, may be within a certain predetermined range. This predetermined range may provide improved uniformity and / or yield of the progeny radionuclide coated on the interior surface of the container or other collection surface after exposure to the precursor radionuclide source. Of course, other constructions using other types of collection surfaces including flowbased generators may also be used.

[0036] In some embodiments, it may be desirable to control both the environment and the ratio between the source and interior surface, or other collection surface, areas, as doing so may improve the yield of progeny radionuclides obtained from the precursor radionuclides of the precursor radionuclide source in the system. Accordingly, in some embodiments, the environment in which the precursor radionuclide of the precursor radionuclide source decays is controlled, while the ratio of the precursor radionuclide source surface area and container interior surface area are also selected to be within a desired range.

[0037] The humidity of the environment in which the system operates may be controlled to be at any suitable humidity, in accordance with any of the embodiments disclosed herein. It will be understood that, in some embodiments described herein, humidity refers to the absolute humidity of the environment in which the radionuclide generator operates. For example, in some embodiments, the absolute humidity may be controlled to be greater than or equal to 0.1 gDBl / 167702246.1 6Atty. Dkt. No.: 137664-5012-WOH2O / 1113of gas (g / m3), greater than or equal to 0.12 g / m3, greater than or equal to 0.14 g / m3, greater than or equal to 0.16 g / m3, greater than or equal to 0.18 g / m3, greater than or equal to 0.2 g / m3, greater than or equal to 0.22 g / m3, greater than or equal to 0.24 g / m3, greater than or equal to 0.26 g / m3, greater than or equal to 0.28 g / m3, greater than or equal to 0.3 g / m3, greater than or equal to 0.32 g / m3, greater than or equal to 0.34 g / m3, greater than or equal to 0.36 g / m3, or greater than or equal to 0.38 g / m3when operating the radionuclide generator. In some embodiments, the absolute humidity may be controlled to be less than or equal to 0.4 g / m3, less than or equal to 0.38 g / m3, less than or equal to 0.36 g / m3, less than or equal to 0.34 g / m3, less than or equal to 0.32 g / m3, less than or equal to 0.3 g / m3, less than or equal to 0.28 g / m3, less than or equal to 0.26 g / m3, less than or equal to 0.24 g / m3, less than or equal to 0.22 g / m3, less than or equal to 0.2 g / m3, less than or equal to 0.18 g / m3, less than or equal to 0.16 g / m3, less than or equal to 0.14 g / m3, or less than or equal to 0.12 g / m3when operating the radionuclide generator. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 0.1 g / m3and less than or equal to 0.4 g / m3or greater than or equal to 0.14 g / m3and less than or equal to 0.35 g / m3or greater than or equal to 0.16 g / m3and less than or equal to 0.32 g / m3. Other ranges and combinations of ranges are also possible. An appropriate method for measuring the absolute humidity of an environment may include measuring humidity and / or temperature using one or more appropriate sensors installed within the environment.

[0038] In some embodiments, humidity refers to the relative humidity of the environment in which the radionuclide generator operates. For instance, in some embodiments, the relative humidity of the environment is greater than or equal to 5%, greater than or equal to 8%, greater than or equal to 10%, greater than or equal to 20%, greater than or equal to 30%, greater than or equal to 40%, greater than or equal to 50%, greater than or equal to 60%, greater than or equal to 70%, greater than or equal to 80%, or greater than or equal to 90%. In some embodiments, the relative humidity of the environment is less than or equal to 98%, less than or equal to 90%, less than or equal to 80%, less than or equal to 70%, less than or equal to 60%, less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, less than or equal to 20%, less than or equal to 10%, or less than or equal to 8%. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 5% and less than or equal to 98%). Other ranges and combinations of ranges are also possible.DBl / 167702246.1 7Atty. Dkt. No.: 137664-5012-WO

[0039] The temperature of the environment in which the radionuclide generator operates may be controlled to be at any suitable temperature, in accordance with any of the embodiments disclosed herein. For example, in some embodiments, the temperature may be controlled to be greater than or equal to 10 degrees C, greater than or equal to 11 degrees C, greater than or equal to 12 degrees C, greater than or equal to 13 degrees C, greater than or equal to 14 degrees C, greater than or equal to 15 degrees C, greater than or equal to 16 degrees C, greater than or equal to 17 degrees C, greater than or equal to 18 degrees C, or greater than or equal to 19 degrees C when operating the radionuclide generator. In some embodiments, the temperature may be controlled to be less than or equal to 20 degrees C, less than or equal to 19 degrees C, less than or equal to 18 degrees C, less than or equal to 17 degrees C, less than or equal to 16 degrees C, less than or equal to 15 degrees C, less than or equal to 14 degrees C, less than or equal to 13 degrees C, less than or equal to 12 degrees C, or less than or equal to 11 degrees C when operating the radionuclide generator. Combinations of the foregoing ranges are possible (e g., greater than or equal to 10 degrees C and less than or equal to 20 degrees C or greater than or equal to 12 degrees C and less than or equal to 20 degrees C or greater than or equal to 11 degrees C and less than or equal to 20 degrees C or greater than or equal to 18 degrees C and less than or equal to 22 degrees C or greater than or equal to 16 degrees C and less than or equal to 20 degrees C or greater than or equal to 17 degrees C and less than or equal to 20 degrees C). Other ranges and combinations of ranges are also possible.

[0040] In the various embodiments disclosed herein, a precursor radionuclide source may have any suitable source surface area, in some embodiments. The source surface area, in some embodiments, includes the surface area of the precursor radionuclide source exposed to the environment. The source surface area may be determined using the geometric surface area of the source before deposition of the radionuclide thereon, in accordance with some embodiments. In some embodiments, the source surface area is greater than or equal to 1 cm2, greater than or equal to 2 cm2, greater than or equal to 3 cm2, greater than or equal to 4 cm2, greater than or equal to 5 cm2, greater than or equal to 6 cm2, greater than or equal to 7 cm2, greater than or equal to 8 cm2, greater than or equal to 9 cm2. . In some embodiments, the source surface area is less than or equal to 10 cm2, less than or equal to 9 cm2, less than or equal to 8 cm2, less than or equal to 7 cm2, less than or equal to 6 cm2, less than or equal to 5 cm2, less than or equal to 4 cm2, less than or equal to 3 cm2, or less than or equal to 2 cm2. Combinations of the foregoingDBl / 167702246.1 8Atty. Dkt. No.: 137664-5012-WOranges are possible (e.g., greater than or equal to 1 cm2and less than or equal to 10 cm2). Other ranges and combinations of ranges are also possible.

[0041] In the various embodiments disclosed herein, a container, or other collection surface, may have any suitable collection surface area. The collection surface area, in some embodiments, includes the surface area of the one or more surfaces of the container or other structure that define the volume configured to be exposed to the precursor radionuclide source and coated by any progeny radionuclides therefrom. The collection surface area may be determined using the geometric surface area of the one or more surfaces that define the volume of the container or other collection chamber. In some embodiments, the collection surface area is greater than or equal to 50 cm2, greater than or equal to 60 cm2, greater than or equal to 70 cm2, greater than or equal to 80 cm2, greater than or equal to 90 cm2, greater than or equal to 100 cm2, greater than or equal to 110 cm2, greater than or equal to 120 cm2, or greater than or equal to 130 cm2. In some embodiments, the collection surface area is less than or equal to 140 cm2, less than or equal to 130 cm2, less than or equal to 120 cm2, less than or equal to 110 cm2, less than or equal to 100 cm2, less than or equal to 90 cm2, less than or equal to 80 cm2, less than or equal to 70 cm2, or less than or equal to 60 cm2. Combinations of the foregoing ranges are possible (e.g. greater than or equal to 50 cm2and less than or equal to 140 cm2). Other ranges and combinations of ranges are also possible.

[0042] The ratio of the source surface area of the precursor radionuclide source to the collection surface area of the container may be any suitable ratio. For example, in some embodiments, the ratio of the source surface area of a precursor radionuclide source to the surface area of a collection surface is greater than or equal to 1 :25, greater than or equal to 1 :30, greater than or equal to 1 :40, greater than or equal to 1:50, greater than or equal to 1 :60, greater than or equal to 1 :70, greater than or equal to 1 :80, greater than or equal to 1 :90, greater than or equal to 1 : 100, greater than or equal to 1 : 120, greater than or equal to 1 : 140, greater than or equal to 1 : 160, greater than or equal to 1 : 180, greater than or equal to 1 :200, greater than or equal to 1 :220, greater than or equal to 1 :240, or greater than or equal to 1 :260. In some embodiments, the ratio of the source surface area of a precursor radionuclide source to the surface area of a collection surface is less than or equal to 1 :280, less than or equal to 1 :260, less than or equal to 1 :240, less than or equal to 1 :220, less than or equal to 1 :200, less than or equal to 1:180, less than or equal to 1:160, less than or equal to 1:140, less than or equal to 1:120, lessDBl / 167702246.1 9Atty. Dkt. No.: 137664-5012-WOthan or equal to 1 : 100, less than or equal to 1 : 90, less than or equal to 1 :80, less than or equal to 1 :70, less than or equal to 1 :60, less than or equal to 1:50, less than or equal to 1 :40, or less than or equal to 1 :30. Combinations of the foregoing ranges are possible including (greater than or equal to 1 :25 and less than or equal to 1 : 280). Other ranges and combinations of ranges are also possible.

[0043] In some embodiments, one or more progeny radionuclides (e.g., a grand-progeny radionuclide of a precursor radionuclide) may be collected in any suitable yield using any of the systems described herein. In some embodiments, a yield may be expressed as a percentage of a theoretical maximum yield, i.e., an amount of progeny radionuclides obtained relative to an expected amount from a known amount of parent radionuclides.

[0044] For instance, in some embodiments, the one or more progeny radionuclides may be collected on one or more surfaces at least partially defining the interior volume of a container in an amount of greater than or equal 10%, greater than or equal 20%, greater than or equal 30%, greater than or equal 40%, greater than or equal 50%, greater than or equal to 55%, greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, or greater than or equal to 75% of a theoretical maximum yield. In some embodiments, the one or more progeny radionuclides may be collected on one or more surfaces at least partially defining the interior volume of a container in an amount of less than or equal to 80%, less than or equal to 75%, less than or equal to 70%, less than or equal to 65%, less than or equal to 60%, less than or equal to 55%, less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, or less than or equal to 20% of a theoretical maximum yield. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 10% and less than or equal to 80%).

[0045] Also for instance, in some embodiments, the one or more progeny radionuclides may be collected on one or more surfaces at least partially defining the interior volume of a container in an amount of greater than or equal to 10%, greater than or equal to 20%, greater than or equal to 30%, greater than or equal to 40%, greater than or equal to 50%, greater than or equal to 55%, greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, or greater than or equal to 75% of a theoretical maximum yield throughout the entire lifetime of the generator (e.g., the time from the beginning of the initial exposure of the precursor radionuclide source to one or more surfaces at least partially defining the interior volume of the container to the end of the final such exposure of the same precursor radionuclide source). InDBl / 167702246.1 10Atty. Dkt. No.: 137664-5012-WOsome embodiments, the one or more progeny radionuclides may be collected on one or more surfaces at least partially defining the interior volume of a container in an amount of greater than or equal to 40% or greater than or equal to 50%, throughout the entire lifetime of the generator. Other ranges and combinations of ranges are also possible. In some embodiments, the lifetime of the generator (e.g., the time from the beginning of the initial exposure of the precursor radionuclide source to one or more surfaces at least partially defining the interior volume of the container to the end of the final such exposure of the same precursor radionuclide source) is at least 10 days, at least 20 days, at least 30 days, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 12 months, or at least 1 year. In some embodiments, the lifetime of the generator is less than 10 days, less than 20 days, less than 30 days, less than 1 month, less than 2 months, less than 3 months, less than 4 months, less than 5 months, less than 6 months, less than 7 months, less than 8 months, less than 9 months, less than 10 months, less than 12 months, or less than 1 year. Combinations of the foregoing are possible (e.g., at least 20 days and less than 1 year, at least 1 month and less than 1 year, at least 20 days and less than 6 months, at least 1 month and less than 6 months, at least 20 days and less than 5 months, at least 1 month and less than 5 months, at least 20 days and less than 4 months, at least 1 month and less than 4 months, at least 20 days and less than 3 months, at least 1 month and less than 3 months). Other ranges and combinations of ranges are also possible.

[0046] In some embodiments, one or more progeny radionuclides may be collected in any suitable purity on a collection surface (e.g., an interior surface area of a container) using any of the systems described herein. For instance, in some embodiments, one or more progeny radionuclides may be collected in a purity of greater than or equal to 90%, greater than or equal to 95%, greater than or equal to 99%, greater than or equal to 99.9%, greater than or equal to 99.99%, or greater than or equal to 99.999%. In some embodiments, one or more progeny radionuclides may be collected in a purity of less than or equal to 99.9999%, less than or equal to 99.999%, less than or equal to 99.99%, less than or equal to 99.9%, less than or equal to 99%, or less than or equal to 95%. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 90% and less than or equal to 99.9999% or greater than or equal to 99% and less than or equal to 99.9999%). Other ranges and combinations of ranges are also possible.DBl / 167702246.1 11Atty. Dkt. No.: 137664-5012-WO

[0047] The radionuclide generators described herein may generally include a precursor radionuclide source comprising precursor radionuclides configured to decay into gaseous progeny radionuclides. The radionuclide generator may further include a container or other collection chamber configured to receive the progeny radionuclides and / or grand-progeny radionuclides. In some embodiments, the container or other chamber includes one or more collection surfaces defining the volume into which the one or more progeny radionuclides are emanated or otherwise collected. In some embodiments, the radionuclide generator includes a precursor radionuclide source including a precursor radionuclide configured to decay into gaseous progeny radionuclides, some of which emanate to the one or more collection surfaces of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide that may be collected thereon.

[0048] While several embodiments related to static emanation-based generators are described herein, it should be understood that the disclosed system and methods are not so limited. For example, in some embodiments, the systems and methods disclosed herein may be used for generating radionuclides a flow-type generator. For instance, in some embodiments, the system may include a pressurized gas source (e.g., pressurized gas cylinders, pumps, etc.) fluidically connected to the precursor radionuclide source and configured to flow gas from the precursor radionuclide source towards a desired collection surface. In some such embodiments, the precursor radionuclide decays into a gaseous progeny radionuclide, which are transported to the collection surface by the associated flow of gas. The one or more progeny radionuclides contained in the gas flow may then decay into grand-progeny radionuclides and / or otherwise be collected downstream, e.g., within a container, a liquid, or the like.

[0049] The systems and methods disclosed herein for generating radionuclides may include the use of an environmental controller, in accordance with some embodiments. The environmental controller, in some embodiments, is configured to control one or more parameters of the environment during generation of one or more progeny radionuclides. For example, the one or more parameters to be controlled by the environmental controller may include the temperature, the humidity, the electrostatic charge, the gas pressure, and / or the gas composition within the environment (e.g., controlling the compositions of the gas other than the water content), in accordance with some embodiments. The environmental controller, in some embodiments, comprises a temperature controller and / or a humidity controller.DBl / 167702246.1 12Atty. Dkt. No.: 137664-5012-WO

[0050] In some embodiments, an environmental controller may control the environment in which the container and / or the precursor radionuclide source is contained, e.g., before, during, and / or after exposure of the precursor radionuclide source to the interior volume of the container. In some embodiments, the environmental controller is a humidor chamber, a temperature- controlled chamber, a vacuum chamber, a glovebox, combinations of the foregoing, and / or other appropriate constructions. In other embodiments, the environmental controller may be integrated with a radionuclide generator, associated with a container or other collection chamber, or otherwise arranged to control one or more environmental parameters associated with the precursor radionuclide source and / or the chamber exposed to the emanated one or more progeny radionuclides. Thus, an environmental controller may include a temperature controller including, but not limited to, thermoelectric devices, resistive heaters, refrigeration cycles, heat exchangers fluidly coupled to an appropriate heating or cooling reservoir, and / or any other appropriate heater and / or cooler. An environmental controller may additionally or alternatively include a humidity controller including, but not limited to, a humidor chamber, a moisture source, and / or a desiccant. In some embodiments, the humidity controller is configured to increase the absolute humidity and / or relative humidity in a volume to be within a predetermined humidity range. In some embodiments, the humidity controller is configured to decrease the absolute humidity and / or relative humidity in a volume to be within a predetermined humidity range. In some embodiments, the environmental controller is configured to control an electrostatic charge, a gas composition, and / or a gas pressure. It will be understood that an electrostatic charge within an environment may be at least partially controlled by controlling the humidity of the environment using the environmental controller. In some embodiments, one or more components of the environmental controller may be electrically isolated and / or electrically grounded to provide control over the electrostatic charge within the environment. In some embodiments, the environmental controller may include a gas source (e g., an inert gas source or a source of gas to which a gaseous radionuclide such as radon may adhere) and regulator. In some embodiment, the environmental controller includes a gas pump and / or a vacuum source in fluidic communication with the environment to control a gas pressure of the environment. Non-limiting examples of vacuum sources include a water aspirator, a steam ejector, an air ejector, a positive displacement pump, and / or any other appropriate vacuum source. In some cases, the various environmental controllers (e.g., a humidity, electrostatic charge, gas pressure, gas composition, and / orDBl / 167702246.1 13Atty. Dkt. No.: 137664-5012-WOtemperature controller) may be operated to provide environmental parameters within a desired volume to be within the parameter ranges disclosed herein to facilitate improved yields of one or more desired progeny radionuclides.

[0051] In some embodiments, a radionuclide generator may include one or more sensors. For example, in some embodiments, the one or more sensors may be configured to measure one or more parameters of an environment present in the interior volume of a container or other chamber including a collection surface. For example, the one or more sensors may be configured to measure one or more parameters of an environment in which the precursor radionuclide of the precursor radionuclide source decays and / or where the one or more progeny radionuclides are collected. In some embodiments, this may be the same volume and environment. The one or more parameters may include the temperature, a humidity, a gas composition, a gas flow rate into and / or out of a volume configured to receive the progeny radionuclides, or any other suitable parameter that provides information regarding the environment. The one or more sensors, in some embodiments, a radionuclide generator may include a temperature sensor, a humidity sensor, a gas flow sensor, combinations of the foregoing, and / or any other appropriate sensors. In some embodiments, the radionuclide generator includes a temperature sensor and a humidity sensor. In such embodiments, signals from the one or more sensors may be used to control an associated environmental controller of the radionuclide generator to maintain a desired environmental parameter to be within the above noted predetermined ranges (e.g., humidity, temperature, and / or any other appropriate environmental parameter).

[0052] The system, in some embodiments, may include one or more processors. The one or more processors can have associated non-transitory memory that include computer-readable instructions that, when executed, cause the one or more processors to control one or more parameters of the environment of the system for generating radionuclides. For instance, in some embodiments, the one or more processors may be configured to output control signals to heat and / or cool the environment of the system for generating radionuclides, e.g., using a temperature controller. In some embodiments, the one or more processors may be configured to output control signals to control a humidity of the environment of the system for generating radionuclides, e.g., using a humidity controller.

[0053] It will be further understood that while embodiments related to actively controlled environments are detailed above and elsewhere herein, the environment in which the precursorDBl / 167702246.1 14Atty. Dkt. No.: 137664-5012-WOradionuclides of the precursor radionuclide source are configured to decay may be altered prior to introduction to the system. For instance, the environment of the system, e.g., the interior volume of a container or other collection chamber, may be controlled prior to exposing the interior volume to the precursor radionuclides of the precursor radionuclide source. For example, the interior volume of a container may be modified or otherwise controlled prior to being connected to a radionuclide generator. In some such embodiments, a container may be heated, cooled, and / or moisture may be added or removed from the interior volume of the container, prior to introducing the container to a system. In some embodiments, one or more surfaces of the container that at least partially define the interior volume may be preconditioned with a compound configured to remove and / or introduce water over time. In some embodiments, the compound may be coated on the one or more surfaces. Non-limiting examples of compounds include desiccants for removing moisture and / or polymers like polyethylene glycol (PEG) for introducing moisture.

[0054] Turning to the figures, specific non-limiting embodiments are described in further detail. It should be understood that the various systems, components, features, and methods described relative to these embodiments may be used either individually and / or in any desired combination as the disclosure is not limited to only the specific embodiments described herein.

[0055] FIG. 1 depicts a diagram of an exemplary thorium series decay chain beginning with thorium 232 (232Th). The half-life of each radionuclide in the decay chain is noted in the figure. Note that the radon 220 radionuclide (220Rn) rapidly decays (e.g., a half-life of 55.6 seconds) into polonium 216 (216Po), which further quickly decays (e.g., a half-life of 0.145 seconds) into a lead 212 radionuclide (212Pb). It will further be noted from FIG. 1 that220Rn may be a gas at ambient pressure and temperature. Accordingly, it will be appreciated that when a source including a precursor radionuclide to220Rn (e.g.,224Ra,228Th,228Ra,232Th, or228Ac) is exposed (e.g., an interior surface), the precursor radionuclide may decay into a gaseous radionuclide such as220Rn. The gaseous220Rn may then decay into (e.g., via216Po)212Pb and may deposit onto the exposed portion of the container as212Pb. Note that the materials described in FIG.l are exemplary, and that the system described herein is suitable for use with any radionuclide-generating material and radionuclide generator wherein a container or other collection surface is exposed to collect progeny radionuclides from the precursor radionuclide material of the generator for the subsequent use of the progeny radionuclides. In someDBl / 167702246.1 15Atty. Dkt. No.: 137664-5012-WOembodiments of the systems and methods described herein, the precursor radionuclide comprises thorium and / or radium, the gaseous progeny radionuclide comprises radon, and / or the grandprogeny radionuclide comprises polonium and / or lead.

[0056] In some embodiments, the precursor radionuclide source may have any suitable radioactivity. For instance, in some embodiments, the radioactivity of the precursor radionuclide source is selected to provide a certain amount of one or more progeny radionuclide from the precursor radionuclide source in a certain amount of time. In some embodiments, the radioactivity of the precursor radionuclide source is greater than or equal to 1 kBq, greater than or equal to 10 kBq, greater than or equal to 100 kBq, greater than or equal to 1 MBq, greater than or equal to 10 MBq, greater than or equal to 100 MBq, or greater than or equal to 500 MBq, or greater than or equal to 1 GBq. In some embodiments, the radioactivity of the precursor radionuclide source is less than or equal to 10 GBq, less than or equal to 1 GBq, less than or equal to 500 MBq, less than or equal to 100 MBq, less than or equal to 10 MBq, less than or equal to 1 MBq, less than or equal to 100 kBq, or less than or equal to 1 kBq. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 1 kBq and less than or equal to 10 GBq, or greater than or equal to 1 kBq and less than or equal to 1 GBq, or greater than or equal to 500 MBq and less than or equal to 10 GBq). In some embodiments, the radioactivity of the precursor radionuclide source is greater than greater than 500 MBq, greater than 600 MBq, greater than 700 MBq, greater than 800 MBq, greater than 900 MBq, greater than 1 GBq, greater than 1.5 GBq, greater than 2 GBq, or greater than 2.5 GBq, In some embodiments, the radioactivity of the precursor radionuclide source is greater than greater than 500 MBq, In some embodiments, the radioactivity of the precursor radionuclide source is greater than or equal to 500 MBq and less than or equal to 2.5 GBq, greater than or equal to 500 MBq and less than or equal to 2 GBq, or greater than or equal to 500 MBq and less than or equal to 1.5 GBq, In some embodiments, the radioactivity of the precursor radionuclide source is greater than or equal to 500 MBq and less than or equal to 1.5 GBq. Other ranges and combinations of ranges are also possible.

[0057] In some embodiments, the radioactivity of the precursor radionuclide source may provide a therapeutically effective does of the one or more progeny radionuclides. For instance, in some embodiments, the therapeutically effective dose of the one or more progeny radionuclides has a radioactivity of greater than or equal to 10 MBq, greater than or equal to 50DBl / 167702246.1 16Atty. Dkt. No.: 137664-5012-WOMBq, greater than or equal to 100 MBq, greater than or equal to 150 MBq, greater than or equal to 200 MBq, or greater than or equal to 250 MBq. In some embodiments, the therapeutically effective dose of the one or more progeny radionuclides has a radioactivity of less than or equal to 300 MBq, less than or equal to 250 MBq, less than or equal to 200 MBq, less than or equal to 150 MBq, less than or equal to 100 MBq, or less than or equal to 50 MBq. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 10 MBq and less than or equal to 300 MBq, or greater than or equal to 50 MBq and less than or equal to 250 MBq). Other ranges and combinations of ranges are also possible.

[0058] FIGS. 2A-2B show cutaway views of one embodiment of a system configured for generating radionuclides 100, where the system 100 may be configured to receive a container 112, e.g., within a container receptacle 114. The container receptacle 114 may be configured to receive the container 112, for example by including a cavity sized and shaped to receive the container. The system 100 may further be configured to move the container 112 within the container receptacle 114, for example, between various poses within the container receptacle. For example, a container 112 may be loaded into the system 100 in a first pose (e.g., the position and orientation of the container in FIG. 2A) and moved into a second pose (e.g., the position and orientation of the container in FIG. 2B). In the first pose, the container may be positioned and / or oriented to be loaded into or unloaded from the generator, for example by aligning the container (or a portion thereof, such as an opening, a neck, a rim, or any other appropriate portion) with a loading port of the generator. In the second pose, the container may be positioned and / or oriented to selectively receive a precursor radionuclide source through the opening of the container into an interior volume of the container. In some embodiments, when the container is in the second pose, the container and / or an opening thereof may be aligned with a precursor radionuclide source and / or with a portion of a source holder 110 (e.g., a shaft, a sheath, or another portion of a source module). In some embodiments, the container 112 may be fluidically coupled to the precursor radionuclide source 132.

[0059] The source holder 110 may be configured to receive a precursor radionuclide source 132 (the dashed lines in the views of FIGS. 2A-2B denoting internal structures). In some embodiments, the source holder 110 includes a shaft 134 on which the precursor radionuclide source 132 is disposed. The source holder 110 may further be configured to selectively expose an interior surface of the container 112 to the precursor radionuclide source in an exposedDBl / 167702246.1 17Atty. Dkt. No.: 137664-5012-WOconfiguration and isolate the interior surface of the container from the precursor radionuclide source in an isolated configuration. For example, the shaft 134 may be selectively extendable and retractable, such that the source holder 110 may be configured to move the source 132 between a retracted configuration in which the source 132 is isolated from the container 112 (e.g., the configuration of FIG. 2A) and an extended configuration in which the interior surface of the container 112 is exposed to the source 132 (e.g., the configuration of FIG. 2B). In other words, an exposed configuration may be an extended configuration, and / or an isolated configuration may be a retracted configuration, although exposed and isolated configurations may additionally or alternatively correspond to other arrangements. In some embodiments, the shaft may include a handle 120 to facilitate movement of the source 132 between the retracted and extended configurations, for example in the directions of arrow 136. When the source holder 110 is in the extended configuration and the precursor radionuclide source is exposed to one or more collection surfaces (e g., interior surfaces) defining the interior volume of the container 112. The source holder 110 may include a seal such that a gas-tight seal 140 forms between the source holder and the container. Accordingly, the precursor radionuclide source 132 of the source holder 110 may decay into a gaseous progeny radionuclide that emanates into the interior volume and contacts the one or more surfaces of the container 110. Upon further decay of the gaseous progeny radionuclide a solid radionuclide (e.g., lead and / or polonium) may deposit onto the collection surface.

[0060] In some embodiments, the time that the212Pb precursor isotope source is kept in the container can be at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least a year. In some embodiments, the use life of the212Pb precursor isotope source is at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least a year.

[0061] While the exemplary embodiments shown in FIGS. 2A-2B illustrate a system configured such that progeny radionuclides from the precursor radionuclide source emanate from the source and deposit into the container, as noted previously, other systems with other types of generator configurations are also contemplated. For instance, flow-based systems where a precursor radionuclide source comprising precursor radionuclides configured to decay into gaseous progeny radionuclide includes a gas source fluidically connected to the precursorDBl / 167702246.1 18Atty. Dkt. No.: 137664-5012-WOradionuclide source and a collection surface may be used in some embodiments. In some such embodiments, the gas source is configured to flow gas to collect any gaseous progeny radionuclide and to carry them downstream to a volume including a collection surface (e.g., a container, a capture fluid, or any other surface or material suitable for collecting the gaseous progeny radionuclide).

[0062] FIGS. 2A-2B further depicts one or more sensors 172 configured to measure one or more parameters of the environment in which the precursor radionuclide source 132 is configured to decay (e.g., the interior volume of the container 112 and / or a volume in which the precursor radionuclide source 132 is located during collection). The one or more sensors 172 may be configured to sense one or more parameters of the environment, such as a temperature and / or a humidity. The system further includes an environmental controller 174 that is configured to control the environment present within the interior volume of the container 112 and / or within an environment in which the precursor radionuclide source 132 is located during collection. In the depicted embodiment, the precursor radionuclide source 132 is disposed in the interior volume of the container 112 during collection, though sensing and control of separate volumes associated with both are also contemplated. As noted above, the environmental controller 174 may include a temperature controller and / or a humidity controller, in accordance with some embodiments. As illustrated, the one or more sensors 172 and the environmental controller 174 may be in communication with one or more processors 176 configured to receive signals from the one or more sensors 172 and control the environmental controller 174 to maintain at least one of the one or more parameters within a predetermined operating range as noted previously.

[0063] In some embodiments the one or more processors 176 may be in wired or wireless communication with the one or more sensors 172 and / or environmental controller 174. For example, as illustrated, the one or more processors 176 may be located external to the system in which the precursor radionuclide source 132 is exposed to the container 112, and thus in wireless communication with the one or more sensors 172 and the environmental controller 174. In some embodiments, the one or more processors 176 may be wireless and located internal to the system, and / or may be in wired communication with the one or more sensors 172 and / or the environmental controller 174. The one or more processors 176 can have associated non- transitory memory that include computer readable instructions that, when executed, cause theDBl / 167702246.1 19Atty. Dkt. No.: 137664-5012-WOone or more processors 176 to control the environmental controller 174 to operate according to any of the methods disclosed herein. For instance, in some embodiments, the one or more processors 176 may be configured to receive signals from the one or more sensors 172 and control the environmental controller 174 to maintain at least one parameter of the environment within the interior volume of the container 112 or other volume associated with a collection surface and / or precursor radionuclide source 132 to be within a desired operating range during generation and collection of the one or more progeny radionuclides.

[0064] Furthermore, as depicted, the system 110 may be contained within a chamber 170, which may be configured to control one or more parameters of the environment of the system. For instance, chamber 170, in some embodiments, may either include, or may be, an environmental controller such as a humidor chamber, a temperature controlled chamber, and / or other appropriate type of chamber including a controlled environment in which the precursor radionuclide source 132 and the container 112 may be positioned to provide a desired humidity and / or temperature during generation and collection of the one or more progeny radionuclides.

[0065] FIGS. 2C-2D depict cross-sections of one exemplary embodiment of the source holder 110 of FIGS. 2A-2B. FIG. 2C depicts the source 132 in an extended configuration, while FIG. 2C depicts the 2D source 132 in a retracted configuration. In some embodiments, a shaft of a source holder 110 may include multiple components. For example, the shaft may include a rod 156, a sheath 146, a shield element 160, and a source receptacle 162. In some embodiments, the rod 156 may be an elongate member configured to extend from a distal end portion 144 of the source module 110 toward the proximal end portion 142. Additionally, the rod 156 may include or may be coupled to a source handle 120 at a distal end of the rod to allow the shaft (or a rod thereof) to be moved. In some embodiments, a shield 160 may be included in the shaft (e.g., at a distal location relative to the source) in order to at least partially block nuclear radiation from escaping the generator from the source 132. As with other shielding components described herein, a shield element may be formed from any appropriate material, including lead, tungsten, and / or others described herein or otherwise known in the art. A source receptacle 162 may be configured to receive a precursor radionuclide source, for example by including an opening, slot, or other receptacle sized and shaped to receive the source. In the embodiment shown, a recess 258 or other appropriate structure configured to receive the precursor radionuclide source 132 may be formed in the source receptacle 162. For example, the recess 258 may be sized andDBl / 167702246.1 20Atty. Dkt. No.: 137664-5012-WOshaped to receive the source 132, which may be formed as an elongate disc in the embodiment shown. Although the source is depicted as an elongate disc in the embodiment shown, it will be appreciated that a source may be formed in any appropriate regular or irregular geometry, including a cylinder (including an annular cylinder, a solid cylinder, or a combination thereof), a disc, a tablet, a block, a chip, a sphere, a sheet, a plate, a ball, a rod, or any other appropriate geometry.

[0066] The source holder 110 may further include one or more components for controlling one or more parameters of the source and / or an environment in which the source is contained. For instance, source holder 110 may include a channel 164 extending along at least a portion of a length of the source holder 110, and in the depicted embodiment through a portion of a length of the rod 156. The channel 164 may be connected to an environmental controller 174a, such as a humidity controller (e.g., a source of gas with a desired humidity) configured to modify a humidity of the gas flowing into or out of the environment containing the precursor radionuclide source 132. Additionally, or alternatively, to the environmental controller 174a, the source holder 110 may include one or more sensors configured to measure one or more parameters of the gas withdrawn through first channel 164. The source holder 110 may also include an environmental controller 174b and one or more sensors 175 associated with the source receptacle 162. Such features may desirably facilitate measuring and / or controlling one or more parameters of the environment in which the precursor radionuclide source 132 is disposed, e.g., if the source is exposed to the interior volume of a container as shown in FIG. 2B.

[0067] In some embodiments, the source receptacle 162 may be configured to control a temperature of the precursor radionuclide source 132. For example, an environmental controller 174b, such as a temperature controller including any appropriate heater and / or a cooler, may be integrated with or thermally coupled to the source receptacle 162. Alternatively, or additionally, one or more sensors 175 may be associated with the source holder 110 and configured to measure a temperature and / or humidity the precursor radionuclide source is exposed to. In some such embodiments, the one or more sensors 175 may be in wired or wireless communication with the one or more environmental controllers 174a and 174b or other separate environmental controllers.

[0068] FIG. 3 shows an example method flow diagram, in accordance with some embodiments. The depicted method includes controlling an environment present in an interiorDBl / 167702246.1 21Atty. Dkt. No.: 137664-5012-WOvolume defined by a container at 310. Controlling the environment present in an interior volume defined by the container may proceed by any of a variety of suitable methods. For instance, the method may include controlling a temperature of the interior volume of the container.Controlling the temperature, in some embodiments, may include using a temperature controller to heat and / or cool the container and / or the interior volume container therein. The temperature may be controlled within the ranges disclosure elsewhere herein, for instance, to be greater than or equal to 10 degrees C and less than or equal to 20 degrees C.

[0069] In some embodiments, controlling an environment includes controlling a humidity of the interior volume of the container. In some embodiments, controlling the humidity includes adding and / or removing moisture to the interior volume of the container. In some embodiments, controlling the humidity includes injecting water into the interior volume. For example, an aliquot of water may be directly added to the interior volume of the container. In some embodiments, an aqueous solution (e.g., a saturated salt solution) may be contained in and / or exposed to the interior volume of the container, so as to modulate the humidity therein. In some embodiments, humid or dry gas may be flowed through a channel through the precursor radionuclide source holder (e.g., see element 164 in FIGS. 2C-2D) to increase or decrease the humidity of the interior volume of the container, respectively. In some embodiments, the container may be contained within a chamber (e.g., see chamber 170 in FIGS. 2A-2B), and the method may include controlling the environment within the chamber, and as a result controlling the environment contained within the interior volume of the container. In some embodiments, the materials of the container may be varied to control the environment within the interior volume of the container. In some instances, the material of the container may adsorb different amounts of water. For instance, in some embodiments, the container may comprise glass and / or a plastic that adsorbs little water. In some embodiments, one or more interior surfaces of the interior volume of the container may be coated with a polymer (e.g., polyethylene glycol, PEG) and / or a desiccant configured to adsorb water, which may result in a low humidity present within the interior volume of the container. Alternatively, in some such embodiments, heating the container when the desiccant and / or polymer coating has adsorbed water may result in the desiccant and / or polymer releasing water, and thus increasing a humidity within the interior volume of the container. Still other methods of controlling the humidity and / or the temperature within the interior volume of the container are possible, as this disclosure is not so limited. The humidityDBl / 167702246.1 22Atty. Dkt. No.: 137664-5012-WOmay be controlled within the ranges disclosure elsewhere herein, for instance, to be greater than or equal to 0.1 g / m3and less than or equal to 0.4 g / m3.

[0070] In some embodiments, controlling the environment is performed using one or more processors. In some embodiments, controlling the environment is done manually. The method may further include, in accordance with some embodiments, sensing one or more parameters of the environment present in the interior volume of the container. The information of the one or more parameters sensed (e.g., using one or more sensors) may be transmitted as one or more signals to one or more associated processors that are configured to control one or more associated environmental controllers to control the one or more environmental parameters to be within a predetermined range. For instance, in some embodiments, the method includes sensing the humidity in the interior volume and controlling the humidity in the interior volume based at least in part on the sensed humidity. In some embodiments, the method includes sensing the temperature in the interior volume and controlling the temperature in the interior volume based at least in part on the sensed temperature.

[0071] In some embodiments, the method includes exposing one or more surfaces at least partially defining the interior volume of the container to a precursor radionuclide source comprising a precursor radionuclide at 320. In some embodiments, a container may be positioned within or otherwise connected to a system such that the interior volume of the container may be exposed or otherwise fluidly coupled to the precursor radionuclide source. In some embodiments, the method includes inserting the precursor radionuclide source of a radionuclide generator into the interior volume of the container as described previously above. In some instances, the method includes extending a precursor radionuclide source through an opening of the container, thereby exposing the interior volume of the container to the precursor radionuclide source. In some embodiments, when exposing the one or more surfaces of the interior volume of the container to the precursor radionuclide source, the interior volume includes an interior surface area, the precursor radionuclide source includes a source surface area, and a ratio between the source surface area and the interior surface area may be within the previously noted ranges including a ratio that is greater than or equal to 1:25 and less than or equal to 1:280.

[0072] In some embodiments, the method includes emanating a gaseous progeny radionuclide from the precursor radionuclide source into the interior volume of the container atDBl / 167702246.1 23Atty. Dkt. No.: 137664-5012-WO330. The gaseous progeny may then be allowed to decay further into grand-progeny radionuclides at 340. In some embodiments, the method further includes depositing the grandprogeny radionuclides onto the one or more surfaces of the interior volume of container. The grand-progeny radionuclides may be generated in this manner in a high yield and / or high purity as noted previously.EXAMPLESExample 1: Effects of temperature and humidity on emanation yield

[0073] FIGS. 4A-4B are plots showing the emanation yield for a generator including a 100 MBq precursor radionuclide source when the interior volume of the collection container of the generator is exposed to the precursor radionuclide source. FIG 4A shows emanation yield as a function of absolute humidity within the collection container and FIG 4B shows emanation yield as a function of temperature within the collection container. In each trial, the collection container was exposed to the precursor radionuclide source (in this case thorium 228), which was allowed to decay into gaseous progeny radionuclides (in this case radon 220), which emanated, decayed into grand-progeny radionuclides (in this case lead 212), and deposited onto one or more interior surfaces of the container. The emanation yield is the percentage of actual grandprogeny radionuclides (in this case lead 212) obtained relative to the theoretical maximum yield of grand-progeny radionuclides from the precursor radionuclide (in this case thorium 228).

[0074] FIG. 4A shows that as the average absolute humidity generally decreases (e.g., from trial 1 to trial 32), the emanation yield generally increased, with the higher observed yields occurring as the absolute humidity approached and was below 0.4 g / m3. Similarly, in FIG. 4B shows that as the temperature generally decreases (e.g., from trial 1 to trial 32), the emanation yield generally increased. Specifically, as temperatures decreased to and below 20 degrees C, the emanation yield increased from approximately 40% to approximately 60%.

[0075] FIGS. 5A-5B are similar plots to FIGS. 4A-4B, but show the emanation yield as a function of both the absolute humidity and temperature for three different precursor radionuclide sources over time. The average temperature, average relative humidity, and average absolute humidity for each of FIGS. 5A-5B are summarized below in Table 1.

[0076] Table 1: Average temperature, average relative humidity, and average absolute humidity for samples shown in FIGS. 5A-5B.DBl / 167702246.1 24Atty. Dkt. No.: 137664-5012-WOSample Temperature (C) Relative humidity (%) Absolute humidity (g / m3)FIG. 5A 19.09 36 0.32FIG. 5B 18.62 27 0.22

[0077] FIGS. 6A-6C are plots of the emanation yield of various generators over time. In FIG. 6A, water was added to a collection container of the generator that was being exposed to the precursor radionuclide source at the arrows 601 and 602, resulting in decreases of the radionuclide emanation yield. Without wishing to be bound by theory, it is believed the addition of the water to these sources drowned the substrate, which is what led to the decreased emanation yield. In a related result, FIG. 6B shows the emanation yield from a generator over the course of more than 100 days. Initially, at arrow 604, the emanation yield generally decreased over time. Without wishing to be bound by theory, the inventors believe this was a result of a seasonal change, which led to a decreased absolute humidity of the environment (e.g., the interior volume of the container exposed to the source). This is confirmed at arrows 605 and 606, where aliquots of water were added to the container to increase the environmental humidity, which led to the observed increase in emanation yield thereafter. In a related result, FIG. 6C shows for a generator the emanation yield of Pb212over time for a period of more than 200 days. As shown in FIG. 6C, the average yield over this time period was 63% with daily yields of about 60% to about 70%. It has been found that this yield is consistent across loading amounts.Example 2: Controlling and measuring temperature and humidity within the interior volume of a container

[0078] As shown in FIGS. 7A-7B, a container 700 was configured with a temperature sensor and / or a humidity sensor 702 to monitor the temperature and or humidity within the interior volume of the container. This example details methods for monitoring and / or controlling a humidity within the interior volume of the container, which could be used before and / or during exposure to the precursor radionuclide source. FIGS. 7C-7G are plots of the relative humidity and / or the temperature as a function time measured within a container as depicted in FIGS. 7A- 7B, while FIG. 7H is a plot of the relative humidity as a function of the temperature measured within the container.DBl / 167702246.1 25Atty. Dkt. No.: 137664-5012-WO

[0079] FIG. 7C shows the relative humidity and temperature as measured within a glass vial, where no water was added to the vial. In this instance, the temperature was relatively constant, and the relative humidity varied over time. FIG. 7D shows the relative humidity and temperature as measured within a glass vial, where 0.5 microliters of water was added to the vial at the outset. In this instance, the temperature was relatively constant, and the relative humidity decreased over time. FIG. 7E shows the relative humidity and temperature as measured within a glass vial, where aliquots of water were added to the vial at each time denoted with an arrow. In this instance, the temperature was relatively constant, and the relative humidity increased with the addition of the water aliquots, and then gradually decreased over time following the addition of the third and final water aliquot. FIG. 7F shows the relative humidity and temperature as measured within a glass vial, where the glass vial was coated with polyethylene glycol (PEG) and 0.5 microliters of water was added to the vial at the outset. In this instance, the temperature and the relative humidity were relatively constant.

[0080] FIG. 7G shows the relative humidity and temperature as measured within a plastic (polyethylene) vial, where 1 microliter of water was added to the vial at the outset. In this instance, the temperature and the relative humidity were relatively constant, specifically the relative humidity was saturated at approximately 100% over the test period.

[0081] FIG. 7H shows a plot of the relative humidity within the interior of a glass vial as a function of temperature and whether the container was open to an ambient environment. The data indicate that the relative humidity within the interior volume of the container is higher at lower temperatures. Additionally, when the container was open to the ambient environment, the relative humidity of the container is higher at a specific temperature as compared to when the container is closed to an ambient environment.Example 3: Purity of radionuclides from precursor radionuclide source

[0082] A system for generating radionuclides was tested by exposing a 60 MBq precursor radionuclide source comprising precursor radionuclides (thorium 228) to an interior volume of a container. The precursor radionuclide decayed into a gaseous progeny radionuclide (radon 220), which emanated and decayed into a grand-progeny radionuclide (lead 212), and deposited onto one or more surfaces of the interior volume of the container. The resulting grandprogeny radionuclides were then tested to determine their purity (for the presence of otherDBl / 167702246.1 26Atty. Dkt. No.: 137664-5012-WOradionuclides including progeny radionuclides). The purity of each sample is represented as a separate bar in FIG. 8, which shows high purity (greater than 99.9999% purity) for each sample.Example 4: Precursor Radionuclide Source Conditioning

[0083] During repeated emanation from a precursor radionuclide source in a generator, it is often observed that there is a decline in generator performance over time with regards to emanation yield. The yield is measured as the resulting amount of212Pb (fully ingrown) deposited onto the inner vial surface of a 30 mL collection vial, as measured by a dose calibrator. The amount of measured212Pb is reported as a yield of the theoretical maximum available212Pb (corrected for224Ra ingrowth,228Th decay, and212Pb ingrowth) at the point of stop emanation after an emanation lasting typically 24-72 h. In some instances, when a decline in generator performance is observed over several emanations and dips below the 60% yield threshold, a conditioning is performed.

[0084] In this Example, conditioning refers to exposure of a generator precursor radionuclide source and / or collection vial to a volume of water, and unless indicated otherwise, conditioning is conducted by starting a new emanation with a collection vial containing 1 mL of metal free water.

[0085] In various embodiments, the volume of water introduced into the interior volume of the collection vial can vary. For example, the volume of water can be an absolute water volume that ranges from greater than or equal to 0.5 ul to equal to or less than 5 ml, such as ranges from greater than or equal to 0.5 ul, greater than or equal to 0.8 ul, greater than or equal to 1.0 ul, greater than or equal to 2.0 ul, greater than or equal to 2.5 ul, greater than or equal to 3.0 ul, greater than or equal to 4.0 ul, greater than or equal to 5.0 ul, greater than or equal to 7.5 ul, greater than or equal to 10 ul, greater than or equal to 20 ul, greater than or equal to 30 ul, greater than or equal to 40 ul, greater than or equal to 50 ul, greater than or equal to 75 ul, greater than or equal to 100 ul, greater than or equal to 150 ul, greater than or equal to 200 ul, greater than or equal to 250 ul, greater than or equal to 300 ul, greater than or equal to 350 ul, greater than or equal to 400 ul, greater than or equal to 450 ul, greater than or equal to 500 ul, greater than or equal to 750 ul, greater than or equal to 1 ml to equal to or less than 1 ml, equal to or less than 1.5 ml, equal to or less than 2 ml, equal to or less than 2.5 ml, equal to or less than 3 ml, equal to or less than 3.5 ml, equal to or less than 4 ml, equal to or less than 4.5 ml or equal to or less than 5 ml. Other ranges and combinations of ranges are also possible. Also for example, the volumeDBl / 167702246.1 27Atty. Dkt. No.: 137664-5012-WOof water can be based on a ratio of water volume to collection container volume and such ratio can range from 1 : 100,000 to 1:5, such as 1 : 100,000 or 1 :75,000 or 1.50,000 or 1 :25,000 or 1:10,000 or 1:5,000 or 1:2,500 or 1:1,000 or 1:750 or 1:500 or 1:250 or 1:100 or 1:75 or 1:50 or 1:25 or 1:10 or 1:5. Other ratios within the range of from 1:100,000 to 1:5 are also possible.

[0086] The precursor radionuclide source is exposed into this vial for approximately 1 hour before this conditioning emanation is stopped, and the collection vial containing 1 mL water is replaced by a new dry collection vial. A typical 24-72 hour emanation is then started. Usually, conditioning results in a spike in emanation yield that typically lasts from 1-7 days.

[0087] In Figs. 9B-9C, two generators, GEN-B and GEN-C, are displayed with emanation yields over the generator lifetime. The stars on the graphs in Figs. 9B-9C represent a conditioning event. The average increase in emanation yield on the immediate emanation following a conditioning event is +12%.

[0088] The results suggest that the yield gain from a conditioning event is relative, so that if the emanation yield is allowed to decline to a relatively low yield, the subsequent conditioning event will induce a relatively high response in yield increase.

[0089] The results suggest that it is possible to condition too much so that it negatively affects the following emanation yield. For example, GEN-B in the first 28 days it conditioned 8 times out of a total of 16 emanations (50% of total events) and displayed a sudden drop in yield from a high of 83% to a low of 42%. In the following 73-day period the source was emanated 40 times but only conditioned 6 times (15% of total events). The yield stabilized at an average of 64%. GEN-C was conditioned 5 times out of a total of 16 emanations (31% of total events) and was relatively stable at an average of 61% emanation yield.

[0090] The results also suggest that the need for conditioning appears to scale with activity. As shown in Figs. 9A-9C the three generators GEN-A, GEN-B, and GEN-C had precursor radioisotope amounts of 107 MBq, 550 MBq, and 880 MBq respectively. The 107 MBq source did not need to be conditioned at all, while the 550 MBq source thrived at an approximate 15% frequency of conditioning. The 880 MBq source thrived at approximately 31% conditioning frequency.

[0091] It has been observed that most high activity generators experience a yield drop at some point that correlates with a complete lack of or limited response to conditioning events. For example, results in Fig. 10 for generator GEN-D show that during the first 22 days, the yield isDBl / 167702246.1 28Atty. Dkt. No.: 137664-5012-WOabove 60% and responds well to conditioning events. Then, there is a sudden significant drop in performance, and any subsequent attempt at conditioning has almost no positive effect on performance. This phenomenon has been observed in 10+ high activity generators.

[0092] In various embodiments, the timing and / or frequency at which the volume of water is introduced into the interior volume of the collection vial can vary. For example, the volume of water can be introduced into the interior volume of the collection vial at a frequency of equal to and greater than 5% of emanations from a generator to equal to or less than 50% of emanations from a generator, such as for 5% of emanations from a generator or for 10% of emanations from a generator or for 15% of emanations from a generator or for 20% of emanations from a generator or for 25% of emanations from a generator or for 30% of emanations from a generator or for 35% of emanations from a generator or for 40% of emanations from a generator or for 45% of emanations from a generator or for 50% of emanations from a generator. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 5% of emanations from a generator to less than or equal to 50% of emanations from a generator, or greater than or equal to 10% of emanations from a generator to less than or equal to 40% of emanations from a generator, or greater than or equal to 15% of emanations from a generator to less than or equal to 30% of emanations from a generator). Other ranges and combinations of ranges are also possible. Additionally, the frequency at which the volume of water is introduced into the interior volume of the collection vial can vary within any one lifetime of using a particular precursor radionuclide source, such as for 5% of emanations from a generator during the first 10 collections or first 30 days of using a particular precursor radionuclide source followed by for 10% of emanations from the generator during the remainder of the lifetime of using the particular precursor radionuclide source.

[0093] As shown in Fig. 11, emanation yield data was measured for GMP212Pb production from 12 different GMP precursor radionuclide sources. The data show no correlation with temperature and a miniscule correlation with relative humidity (RH) with higher being better. However, these sources have experienced a yield decline and have become nonresponders to conditioning at some point. If the precursor radionuclide sources do not respond to conditioning at some point, it is believed they will also not respond to environmental RH.

[0094] As shown in Figs. 12A-12D multiple tests were performed with a temperature and RH sensor inside a collection vial during emanation. The sensor was connected to a computerDBl / 167702246.1 29Atty. Dkt. No.: 137664-5012-WOlogging data every 5 minutes. The data shows a 30 mL collection vial untreated maintains a constant RH throughout an emanation lasting 20 hours. Whatever the environment RH will be the vial RH. However, if you add 1 pL of metal free water to the inside of the collection vial before the start of emanation the RH jumps up to approximately 95% within the first hour and then starts declining exponentially to 24% within 12 hours. When a similar trial was performed with a plastic collection vial, the RH was at a constant 90%+. The results suggest that the 30 mL glass collection vial absorbs humidity from the air. Adding 0.5 pL to a 30 mL collection vial results in a peak at approximately 60% RH with the same pattern of decline to 25% within 12 hours. When conditioning was performed for 1 hour, then changed to a new dry collection vial and the RH was monitored over time, the same spike in RH of approximately 93% was shown, but a much slower rate of decline to 51% within 12 hours was observed. The results suggest that conditioning results in water being absorbed by the precursor radionuclide source which then equilibrates with the air when changed to a new dry collection vial. The results also suggest that the water absorbed by materials during conditioning is significantly more than 1 pL.

[0095] While the present teachings have been described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to such embodiments or examples. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art. Accordingly, the foregoing description and drawings are by way of example only.

[0096] While several embodiments of the present disclosure have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present disclosure. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present disclosure is / are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the disclosure described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of theDBl / 167702246.1 30Atty. Dkt. No.: 137664-5012-WOappended claims and equivalents thereto, the disclosure may be practiced otherwise than as specifically described and claimed. The present disclosure is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present disclosure.DBl / 167702246.1 31

Claims

Atty. Dkt. No.: 137664-5012-WOCLAIMSWhat is claimed is:

1. A method of generating radionuclides, comprising:controlling an environment present in an interior volume defined by a container; exposing one or more surfaces at least partially defining the interior volume of the container to a precursor radionuclide source comprising a precursor radionuclide; and emanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

2. The method of claim 1, further comprising inserting the precursor radionuclide source into the interior volume of the container.

3. The method of claim 1 or 2, further comprising sensing one or more parameters of the environment present in the interior volume of the container and controlling the environment based at least in part on the sensed one or more parameters.

4. The method of any one of the preceding claims, wherein controlling the environment in the interior volume comprises controlling a temperature of the interior volume of the container.

5. The method of claim 4, wherein controlling the temperature of the interior volume comprises heating and / or cooling the interior volume.

6. The method of claim 4 or 5, wherein the temperature of the interior volume of the container is controlled to be greater than or equal to 10 degrees C and less than or equal to 20 degrees C.

7. The method of any one of the preceding claims, wherein controlling the environment in the interior volume comprises modifying a humidity of the interior volume.DBl / 167702246.1 32Atty. Dkt. No.: 137664-5012-WO8. The method of claim 7, wherein modifying the humidity in the interior volume includes increasing a humidity in the interior volume.

9. The method of claim 7, wherein modifying the humidity in the interior volume includes increasing a humidity in the interior volume to be within a predetermined humidity range.

10. The method of claim 7, wherein modifying the humidity in the interior volume comprises decreasing a humidity in the interior volume.

11. The method of claim 7, wherein modifying the humidity in the interior volume includes decreasing a humidity in the interior volume to be within a predetermined humidity range.

12. The method of any one of claims 7-11, wherein modifying the humidity in the interior volume comprises injecting water into the interior volume.

13. The method of any one of claims 7-11, wherein modifying the humidity in the interior comprises introducing a volume of water into the interior volume.

14. The method of claim 13, wherein the volume of water ranges from greater than or equal to 0.5 ul to equal to or less than 5 ml.

15. The method of claim 13, wherein a ratio of the volume of water to the interior volume ranges from 1:100,000 to 1:5.

16. The method of any one of claims 7-15, wherein modifying the humidity in the interior volume comprises introducing a volume of a liquid into the interior volume concurrently with exposing the one or more surfaces at least partially defining the interior volume to the precursor radionuclide source .DBl / 167702246.1 33Atty. Dkt. No.: 137664-5012-WO17. The method of any one of claims 7-14, wherein modifying the humidity in the interior volume comprises introducing a volume of a liquid into the interior volume prior to exposing the one or more surfaces at least partially defining the interior volume to the precursor radionuclide source.

18. The method of any one of claims 7-17, wherein modifying the humidity in the interior volume comprises exposing the precursor radionuclide source to a volume of a liquid prior to exposing the one or more surfaces at least partially defining the interior volume to the precursor radionuclide source.

19. The method of any one of claims 7-18, wherein modifying the humidity in the interior volume comprises exposing the precursor radionuclide source to an interior volume of a first container comprising a volume of a liquid; isolating the precursor radionuclide source from the interior volume of the first container; exposing the precursor radionuclide source to an interior volume of a second container, optionally wherein the second container does not comprise a volume of the liquid; and emanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the second container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

20. The method of any one of claims 7-19, further comprising sensing the humidity in the interior volume and controlling the humidity in the interior volume based at least in part on the sensed humidity.

21. The method of any one of 7-20, wherein an absolute humidity of the interior volume of the container is controlled to be greater than or equal to 0.1 g / m3and less than or equal to 0.4 g / m3.

22. A method of generating radionuclides, comprising :exposing an interior volume defined by a container to a volume of a liquid; exposing one or more surfaces at least partially defining the interior volume of the container to a precursor radionuclide source comprising a precursor radionuclide; andDBl / 167702246.1 34Atty. Dkt. No.: 137664-5012-WOemanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein23. A method of generating radionuclides, comprising:exposing a precursor radionuclide source comprising a precursor radionuclide to a volume of a liquid;exposing one or more surfaces at least partially defining an interior volume of a container to the precursor radionuclide source; andemanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

24. A method of generating radionuclides, comprising:exposing a precursor radionuclide source comprising a precursor radionuclide to the interior volume of a first container comprising a volume of a liquid;isolating the precursor radionuclide source from the interior volume of the first container;exposing the precursor radionuclide source to the interior volume of a second container;allowing a gaseous progeny radionuclide from the precursor radionuclide source to emanate into the interior volume of the second container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein;allowing the grand-progeny radionuclide to deposit on one or more surfaces at least partially defining the interior volume of the second container.

25. The method of any one of claims 13-24, wherein the liquid is water.

26. The method of any one of the preceding claims, wherein the container includes polyethylene glycol (PEG) disposed on the one or more surfaces.DBl / 167702246.1 35Atty. Dkt. No.: 137664-5012-WO27. The method of any one of the preceding claims, wherein the container comprises a glass and / or a polymer.

28. The method of any one of the preceding claims, wherein the grand-progeny radionuclide is generated on the surface of the container in an amount of greater than or equal to 50% of a theoretical maximum yield.

29. The method of any one of the preceding claims, wherein the grand-progeny radionuclide is generated on the surface of the container in a purity of greater than or equal to 99%.

30. The method of any one of the preceding claims, wherein the precursor radionuclide comprises thorium and / or radium.

31. The method of any one of the preceding claims, wherein the gaseous progeny radionuclide comprises radon.

32. The method of any one of the preceding claims, wherein the grand-progeny radionuclide comprises polonium and / or lead.

33. A system for generating radionuclides, comprising:a precursor radionuclide source comprising a precursor radionuclide and configured to generate gaseous progeny radionuclides, wherein the precursor radionuclide source is configured to be fluidly coupled to an interior volume of a container;one or more sensors configured to measure one or more parameters of an environment present in the interior volume of the container;an environmental controller configured to control at least one of the one or more parameters of the environment present in the interior volume of the container; and at least one processor configured to receive signals from the one or more sensors and control the environmental controller to maintain the at least one of the one or more parameters within a predetermined operating range.DBl / 167702246.1 36Atty. Dkt. No.: 137664-5012-WO34. The system of claim 33, wherein the environmental controller comprises a humidity controller configured to control a humidity of the internal volume.

35. The system of claim 33, wherein the humidity controller is configured to increase the humidity in the interior volume to be within a predetermined humidity range.

36. The system of claim 33 or 34, wherein the humidity controller is configured to decrease the humidity in the interior volume to be within a predetermined humidity range.

37. The system of any one of claims 34-36, wherein the humidity controller is configured to control the absolute humidity of the interior volume of the container to greater than or equal to 0.1 g / m3and less than or equal to 0.4 g / m3.

38. The system of claim 33 or 34, wherein the environmental controller comprises a temperature controller configured to control a temperature of the internal volume.

39. The system of claim 38, wherein the environmental controller comprises a heater and / or cooler.

40. The system of claim 38 or 39, wherein the temperature controller is a heater.

41. The system of any one of claims 38-40, wherein the temperature controller is a cooler.

42. The system of any one of claims 38-41, wherein the temperature controller is configured to control a temperature of the interior volume of the container to be greater than or equal to 10 degrees C and less than or equal to 20 degrees C.

43. The system of any one of claims 33-42, further comprising the container fluidly coupled to the precursor radionuclide source.DBl / 167702246.1 37Atty. Dkt. No.: 137664-5012-WO44. The system of claim 43, wherein the precursor radionuclide source has a surface area, and a ratio between the surface area of the precursor radionuclide source and a surface area of one or more surfaces defining an interior volume of the container is greater than or equal to 1 :25 and less than or equal to 1 :280.

45. The system of claim 43 or 44, wherein the container includes polyethylene glycol (PEG) disposed on one or more surfaces at least partially defining the interior volume.

46. The system of claim 43 or 44, wherein the container comprises a glass and / or a polymer.

47. The system of any one of claims 41-46, wherein the precursor radionuclide source is configured to emanate the gaseous progeny radionuclide to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

48. The system of claim 47, wherein the grand-progeny radionuclide is generated on the surface of the container in an amount of greater than or equal 50% of a theoretical maximum yield.

49. The system of claim 47 or 48, wherein the grand-progeny radionuclide is generated on the surface of the container in a purity of greater than or equal to 99%.

50. The system of any one of claims 47-49, wherein the grand-progeny radionuclide comprises polonium and / or lead.

51. The system of any one of claims 33-50, wherein the precursor radionuclide comprises thorium and / or radium.

52. The system of any one of claims 33-51, wherein the gaseous progeny radionuclide comprises radon.DBl / 167702246.1 38Atty. Dkt. No.: 137664-5012-WO53. A method of generating radionuclides, comprising:exposing one or more surfaces at least partially defining an interior volume of a container to a precursor radionuclide source comprising a precursor radionuclide, wherein the interior volume includes an interior surface area, the precursor radionuclide source includes a source surface area, and a ratio between the source surface area and the interior surface area is greater than or equal to 1 :25 and less than or equal to 1 :280; andemanating a gaseous progeny radionuclide from the precursor radionuclide source to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

54. The method of claim 53, further comprising inserting the precursor radionuclide source of a radionuclide generator into the interior volume of the container.

55. The method of claim 53 or 54, further comprising controlling an environment present in the interior volume defined by the container.

56. The method of claim 55, further comprising sensing one or more parameters of the environment present in the interior volume of the container and controlling the environment based at least in part on the sensed one or more parameters.

57. The method of claim 56, wherein controlling the environment in the interior volume comprises controlling a temperature of the interior volume of the container.

58. The method of claim 56 or 57, wherein controlling the temperature of the interior volume comprises heating and / or cooling the interior volume.

59. The method of any one of claims 56-58, wherein the temperature of the interior volume of the container is controlled to be greater than or equal to 10 degrees C and less than or equal to 20 degrees C.DBl / 167702246.1 39Atty. Dkt. No.: 137664-5012-WO60. The method of claim 56, wherein controlling the environment in the interior volume comprises modifying a humidity of the interior volume.

61. The method of claim 60, wherein modifying the humidity in the interior volume includes increasing a humidity in the interior volume to be within a predetermined humidity range.

62. The method of claim 60, wherein modifying the humidity in the interior volume includes decreasing a humidity in the interior volume to be within a predetermined humidity range.

63. The method of any one of claims 60-62, wherein modifying the humidity in the interior volume comprises injecting water into the interior volume.

64. The method of any one of claims 60-63, further comprising sensing the humidity in the interior volume and controlling the humidity in the interior volume based at least in part on the sensed humidity.

65. The method of any one of claims 60-64, wherein an absolute humidity of the interior volume of the container is controlled to greater than or equal to 0.1 g / m3and less than or equal to 0.4 g / m3.

66. The method of claim 56, wherein controlling the environment comprises exposing the precursor radionuclide source to a volume of liquid.

67. The method of any one of claims 53-66, wherein the method comprises exposing the interior volume of the container to a volume of a liquid, prior to or concurrently with exposing the one or more surfaces at least partially defining the interior volume of the container to the precursor radionuclide source.

68. The method of any one of claims 53-67, wherein the method comprises, prior to exposing the one or more surfaces at least partially defining the interior volume of the container to theDBl / 167702246.1 40Atty. Dkt. No.: 137664-5012-WOprecursor radionuclide source, exposing the precursor radionuclide source to a volume of a liquid.

69. The method of any one of claims 66-68, wherein the liquid is water.

70. The method of any one of claims 53-69, wherein the container includes polyethylene glycol (PEG) disposed on the one or more surfaces.

71. The method of any one of claims 53-70, wherein the container comprises a glass and / or a polymer.

72. The method of any one of claims 53-71, wherein the grand-progeny radionuclide is generated on the surface of the container in an amount of greater than or equal 50% of a theoretical maximum yield.

73. The method of any one of claims 53-72, wherein the grand-progeny radionuclide is generated on the surface of the container in a purity of greater than or equal to 99%.

74. The method of any one of claims 53-73, wherein the precursor radionuclide comprises thorium and / or radium.

75. The method of any one of claims 53-74, wherein the gaseous progeny radionuclide comprises radon.

76. The method of any one of claims 53-75, wherein the grand-progeny radionuclide comprises polonium and / or lead.

77. A system for generating radionuclides, comprising:a precursor radionuclide source having a source surface area and comprising a precursor radionuclide configured to generate gaseous progeny radionuclides; andDBl / 167702246.1 41Atty. Dkt. No.: 137664-5012-WOa container having an opening and one or more surfaces at least partially defining an interior volume that is configured to receive the precursor radionuclide source, wherein the interior volume includes an interior surface area,wherein a ratio between the source surface area and the interior surface area is greater than or equal to 1 :25 and less than or equal to 1 :280.

78. The system of claim 77, wherein the precursor radionuclide source is configured to selectively extend through the opening of the container to expose the one or more surfaces of the container to the precursor radionuclide source.

79. The system of claim 77 or 78, further comprising one or more sensors configured to measure one or more parameters of an environment present in the interior volume of the container.

80. The system of any one of claims 77-79, further comprising an environmental controller configured to control at least one of the one or more parameters of an environment present in the interior volume of the container.

81. The system of claim 80, further comprising at least one processor configured to receive signals from the one or more sensors and control the environmental controller to maintain the at least one of the one or more parameters within a predetermined operating range.

82. The system of claim 80 or 81, wherein the environmental controller comprises a humidity controller configured to control a humidity of the internal volume.

83. The system of claim 82, wherein the humidity controller is configured to increase the humidity in the interior volume to be within a predetermined humidity range.

84. The system of claim 82 or 83, wherein the humidity controller is configured to decrease the humidity in the interior volume to be within a predetermined humidity range.DBl / 167702246.1 42Atty. Dkt. No.: 137664-5012-WO85. The system of any one of claims 82-84, wherein the humidity controller is configured to control the absolute humidity of the interior volume of the container to greater than or equal to 0.1 g / m3and less than or equal to 0.4 g / m3.

86. The system of claim 80 or 81, wherein the environmental controller comprises a temperature controller configured to control a humidity of the internal volume.

87. The system of claim 86, wherein the environmental controller comprises a heater and / or cooler.

88. The system of claim 86 or 87, wherein the temperature controller is a heater.

89. The system of any one of claims 86-88, wherein the temperature controller is a cooler.

90. The system of any one of claims 86-89, wherein the temperature controller is configured to control a temperature of the interior volume of the container to be greater than or equal to 10 degrees C and less than or equal to 20 degrees C.

91. The system of any one of claims 77-90, wherein the precursor radionuclide source is configured to emanate the gaseous progeny radionuclide to the interior volume of the container such that the gaseous progeny radionuclide decays into a grand-progeny radionuclide therein.

92. The system of claim 91, wherein the grand-progeny radionuclide is generated on the surface of the container in an amount of greater than or equal 50% of a theoretical maximum yield.

93. The system of claim 91 or 92, wherein the grand-progeny radionuclide is generated on the surface of the container in a purity of greater than or equal to 99%.

94. The system of any one of claims 77-93, wherein the precursor radionuclide comprises thorium and / or radium.DBl / 167702246.1 43Atty. Dkt. No.: 137664-5012-WO95. The system of any one of claims 77-94, wherein the gaseous progeny radionuclide comprises radon.

96. The system of any one of claims 91-93, wherein the grand-progeny radionuclide comprises polonium and / or lead.DBl / 167702246.1 44

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