Device for receiving a composition comprising a radioisotope

Abstract

A device for receiving a composition comprising a radioisotope, comprises a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; and an insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls, wherein the one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber; and wherein at least one external sub-volume is formed within the interior chamber between the one or more insert walls and the internal surface of the one or more device sidewalls; and wherein the device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes. Alternatively or additionally, a plurality of particles are provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected sub-volumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 µm to 8 mm.

Description

DEVICE FOR RECEIVING A COMPOSITIONCOMPRISING A RADIOISOTOPE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of U.S. Provisional Application Serial No. 63 / 755,703, filed 7 February 2025, the entire contents of which are hereby incorporated by reference herein for any and all purposes.FIELD

[0002] This disclosure relates to devices for receiving a composition comprising a radioisotope and use of such devices for storing a composition comprising a radioisotope, such as a radiopharmaceutical composition.BACKGROUND

[0003] Radioisotopes are increasingly used in various fields, including medical, industrial, and research applications. Radiopharmaceuticals, where radioisotopes are used to provide diagnostic imaging and therapeutic interventions, have provided major advances in diagnosing and treating cancer, brain diseases and cardiovascular diseases. However, there are significant challenges in producing and storing radioactive isotopes, which is limiting their use and availability.

[0004] One such challenge results from radiolysis of compositions comprising the radioisotopes. Radiolysis is molecular decomposition of molecules such as diluents, drug excipients, or reagents and precursor present in compositions with radioisotopes. In particular, radiation from radioactive decay (e.g. alpha, beta, gamma) interacts with these molecules and causes degradation, leading to radiolytic by-products. These by-products can significantly reduce the purity and effectiveness of the compositions. This is particularly true for radiopharmaceuticals, potentially altering the intended biological activity and reducing the accuracy of diagnostic imaging or therapeutic outcomes. Use of lower purity radiopharmaceuticals in molecular imaging (e.g. positron emission tomography (PET) and single-photon emission computed tomography (SPECT)) will reduce image quality and cause unnecessarily high patient radiation dose in both molecular imaging and molecular-targeted radiotherapy. These unwanted effects are driven by increased off-target distribution and the associated suboptimal radiation dosimetry profile.

[0005] Additionally, the formation of radiolytic by-products can present safety risks, as these unintended products may be toxic, radiotoxic or may trigger adverse reactions in patients.

[0006] Radiolysis also occurs during and complicates the synthesis of radiopharmaceuticals, particularly in multi-step production processes where maintaining chemical integrity is critical.The radioisotope labelling step itself can be prone to radiolysis, which may lead to reduced yields, incomplete labelling, or undesirable side reactions. The formation of impurities limits how much radioactivity can be used and the maximum radioactivity concentration that can be achieved at various points in the manufacturing process and in the formulated drug product. Maintaining radiochemical purity is also essential for regulatory approval and clinical use, and the occurrence of radiolysis during synthesis and storage adds complexity to achieving the stringent purity standards required.

[0007] Conventional approaches to avoiding or reducing radiolysis often involve the use of stabilizers or antioxidants to mitigate the effects of radiolysis. These methods have limited success and can, in some cases, introduce additional challenges, particularly in synthesis. Accordingly, the ongoing challenges of radiolysis in both storage and synthesis highlight the need to improve the stability and quality of compositions comprising radioisotopes, including those comprising radiopharmaceuticals.

[0008] There is also a need to ensure that the techniques for reducing radiolysis are practical and do not impede use. For example, to ensure that the compositions comprising radioisotopes can be used in typical settings, such as clinical settings.SUMMARY

[0009] In a first aspect, there is provided a device for receiving a composition comprising a radioisotope. The device comprises a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; and an insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls. The one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber. At least one external subvolume is formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the one or more device sidewalls. The device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes and the device further comprises a composition comprising a radioisotope provided to each internal sub-volume and external sub-volume.

[0010] In a second aspect, there is provided use of a device to receive a composition comprising a radioisotope. The device comprises a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is forreceiving a composition comprising a radioisotope; and an insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls. The one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber. At least one external subvolume is formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the one or more device sidewalls. The device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes.

[0011] In a third aspect, there is provided a device body comprising one or more device walls and an interior chamber delimited at least in part by an interior surface defined by the one or more device walls, wherein the interior chamber is for receiving a composition comprising a radioisotope; a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected sub-volumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 pm to 8 mm; and a composition comprising a radioisotope, wherein the composition is provided in the fluidly connected sub-volumes.

[0012] In a fourth aspect, there is provided a use of a device to receive a composition comprising a radioisotope, the device comprising: a device body comprising one or more device walls and an interior chamber delimited at least in part by an interior surface defined by the one or more device walls, wherein the interior chamber is for receiving a composition comprising a radioisotope; a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected sub-volumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 pm to 8 mm; and a composition comprising a radioisotope, wherein the composition is provided in the fluidly connected sub-volumes.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The present disclosure will now be described in more detail with reference to the accompanying drawings, which are not intended to be limiting.

[0014] FIG. 1A provides a schematic perspective view of a device with an insert array according to aspects of the present disclosure.

[0015] FIG. IB provides a schematic top view of the device of FIG. 1A.

[0016] FIG. 2 A provides a schematic perspective view of another device with an insert array according to aspects of the present disclosure.

[0017] FIG. 2B provides a schematic top view of the device of FIG. 2 A.

[0018] FIG. 3 A provides a schematic perspective view of a device with an insert array according to aspects of the present disclosure and FIG. 3B provides a top view of the device, and

[0019] FIG. 4 provides a schematic top view of another device with an insert array according to aspects of the present disclosure.

[0020] FIG. 5 provides a schematic perspective view of a device with a stack, according to aspects of the present disclosure.

[0021] FIG. 6A provides a schematic perspective view of a device with an insert array.

[0022] FIG. 6B provides a schematic top view of the device.

[0023] FIG. 7 provides a schematic perspective view of a device with an insert array.

[0024] FIG. 8 A provides a schematic perspective view of vial 2 used in Example 1.

[0025] FIG. 8B provides a schematic perspective view of vial 3 used in Example 1.

[0026] FIG. 8C provides a schematic perspective view of vial 4 used in Example 1.

[0027] FIG. 9 is a line graph depicting the results of Example 1.

[0028] FIG. 10 is a line graph depicting the results of Example 2.

[0029] FIG. 11 is a line graph depicting the results of Example 3.DETAILED DESCRIPTION

[0030] There is a need to address the challenges of radiolysis in both storage and synthesis of radioisotopes, including radiopharmaceuticals, so as to improve the stability and quality of the same.

[0031] In a first aspect, there is provided a device for receiving a composition comprising a radioisotope. The device comprises a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; and an insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls. The one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber. At least one external subvolume is formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the one or more device sidewalls. The device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes and the device further comprises a composition comprising a radioisotope provided to each internal sub-volume and external sub-volume.

[0032] This device configuration provides a structural, geometric solution to reduce radiolysis in radioisotope compositions. By dividing the interior chamber into multiple sub-volumes, the insert array limits the interaction between the emitted particles which cause radiolysis and the remainder of the composition. As such, the insert array attenuates the high energy charged particles produced by the emissions to reduce attenuation in the composition, thereby reducing the formation of radiolytic by-products and improving the stability and purity of the composition. Such devices reduce the amount of radiolysis while avoiding many of the drawbacks which can occur with existing methods of reducing radiolysis, as set out in more detail below.

[0033] Reduction of the radiolysis in the device is provided through the use of the insert array. By making geometric changes to / dividing up the interior chamber of the device via the use of the insert array, smaller sub-volumes of fluid are created. Radiolysis occurs through the depositing of emitted particles during decay of the radioisotope into the composition. The provision of smaller sub-volumes of the fluid means that a larger proportion of the emitted particles (such as a, P, y particles) are deposited outside of the composition, instead being deposited into the one or more walls of the insert array and the walls of the device. This reduces the interaction of the emitted particles with the other components of the composition, thereby reducing the ionization of these other components and, hence, radiolysis. Furthermore, the insert array structure further attenuates high energy charged particles produced by radioactive emissions to reduce attenuation in the composition.

[0034] The reduction of radiolysis generally has several significant benefits. It improves the stability of compositions comprising radioisotopes so that the chemical and radiochemical purity of the radiopharmaceutical, and effectiveness of the radiopharmaceutical when used for treatment or imaging is maintained. Generally speaking, this can improve the effectiveness of the compositions, for example in treatments and imaging using radio radiopharmaceuticals, improved stability also results in higher quality radiopharmaceuticals with more predictable and reliable pharmacokinetics, leading to more accurate diagnostic imaging and more effective therapeutic outcomes. It also improves the availability of radioisotope-containing compositions by prolonging the shelf-life of the compositions and increasing the concentration for a given isotope that can be stored and transported within a given time frame.

[0035] The way in which radiolysis is reduced in these devices can provide significant benefits. For example, the use of the insert array can provide significant advantages over existing radiolysis-reduction techniques. The one or more insert walls of the insert array divide the device interior chamber into several sub-volumes, comprised of at least one internal subvolume defined by the insert wall(s) of the insert array and, additionally, at least one externalsub-volume provided between the one or more insert walls of the insert array and the internal surface of the device body defined by the one or more sidewalls, where a plurality of at least one of these types of sub-volume is present. Although, the use of an insert wall providing only an internal volume of the insert (e.g. an internal sub-volume) may still decrease radiolysis but will limit the total volume that the overall device can hold or process. The present insert arrays, the structure and arrangement of which is so as to create multiple sub-volumes within the device including external sub-volumes enclosed between external surfaces of the insert walls and the internal surface of the device body. This may include external sub-volumes formed between plural insert walls and the internal surface of the device body. The composition containing the radioisotope is also provided outside the one or more internal sub-volumes through the further sub-dividing of the interior chamber into one or more external sub-volumes. Providing the composition to the one or more external sub-volumes also provides regions in which radiolysis will be reduced but while also allowing more volume of composition to be held in the device compared to use of enclosed internal sub-volume(s) only. In other words, utilising the regions outside of the insert array maximises the utilisation of the interior chamber by using at least one sub-volume or pocket in which radiolysis is also reduced. This can substantially increase the volume of fluid within the device than would otherwise be available if just relying on internal sub-volumes.

[0036] The use of a structural insert array, as opposed to chemical stabilisers, also allows for a reduction or elimination of the use of conventional methods for reducing radiolysis which themselves can have drawbacks. For example, use of the present device / insert array can avoid the need to alter the composition itself, for example through the inclusion of additives such as radioprotectants. Radioprotectants are sacrificial chemicals which react with radicals produced from radiolysis. These chemicals can complicate formulation, particularly for radiopharmaceuticals as they typically need a defined toxicity profile for use in injectable drug products. Accordingly, avoiding the need for inclusion of radioprotectants can be particularly advantageous for radiopharmaceuticals. For new compositions, the use of the present devices instead of radioprotectants would avoid having to conduct studies into possible interactions between a radioprotectant and the various components of the radiopharmaceutical compositions, reducing the complexity of development and subsequent regulatory approval. Manufacture / synthesis can also be simplified in that it can remove the need for radioprotectants during manufacture or synthesis (which would otherwise interact with the radiopharmaceutical to produce by-products), thereby eliminating a subsequent step of removing the radioprotectants. This also has advantages for synthesis, where typically sacrificial chemicalsare used but then need to be removed after synthesis, for example through filtration, solid phase extraction or chromatography.

[0037] The need for a defined toxicity profile limits radioprotectants quantity / concentration and the limited intrinsic effectiveness of a chemical radioprotectant based on reactivity with single electron species is further limiting.

[0038] The use of the present device / insert array can avoid modification to existing apparatuses and processes for handling the devices. As an example, transportation and handling of radioisotope compositions will often require the device to be used to contain the radioisotope to be validated and certification to be issued. Provision of an insert array into a device which is already part of a validated or certified transportation process would not require the device itself or the apparatuses and processes used to handle the device during manufacture and shipping to be externally modified, which can avoid e.g. re-certification or re-validation of such devices, apparatuses and processes.

[0039] In a second aspect, there is provided use of the device of the first aspect to receive a composition comprising a radioisotope. That is, the device is used to receive a composition comprising a radioisotope. The device may be in accordance with any of the aspects set out herein and the use (which may be a method of using the device to receive and hold a composition) have the same advantages and uses as set out above for the first aspect.

[0040] In a third aspect, there is provided a device for receiving a composition comprising a radioisotope, the device comprising: a device body comprising one or more device walls and an interior chamber delimited at least in part by an interior surface defined by the one or more device walls, wherein the interior chamber is for receiving a composition comprising a radioisotope; a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected sub-volumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 pm to 8 mm; and a composition comprising a radioisotope, wherein the composition is provided in the fluidly connected sub-volumes.

[0041] As with the first and second aspects, this device configuration provides a structural, geometric solution to reduce radiolysis in radioisotope compositions. Such devices also avoid many of the drawbacks which can occur with existing attempts to reduce radiolysis.

[0042] By dividing the interior chamber into multiple sub-volumes using the particles (such as beads or balls), and, in particular, those having the size disclosed herein, the device limits the interaction between emitted particles and the components of the composition. The particles can create small sub-volumes therebetween, of the order of 20 pm to 8 mm, since the size of these sub-volumes is defined in part by the size of the particles. As this is of the order of theaverage range of many particle emissions in water, this which volumes lead to a significant proportion of the emitting particles being deposited into the particles and the device sidewall. Further, even at the higher particle sizes, it has surprisingly been found that the amount of radiolysis is decreased significantly as compared to an empty device (without particles or an insert array) or existing compositions, but without significant impact on the useability of the device as compared to an empty device. This reduces the formation of radiolytic by-products and, therefore, improves the stability and purity of the radioisotope composition. Moreover, the use of the particles of the claimed size means that these will absorb a large proportion of the emitted particles. Accordingly, for the same reasons as the insert array disclosed herein, the particles provide the benefits associated with lower radiolysis, listed above, and in a similar manner.

[0043] The way in which radiolysis is reduced can also provide significant benefits. The use of particles in a stack can provide significant advantages over existing radiolysis -reduction techniques. The use of stacked particles provides the network of interconnected sub-volumes created in voids formed between the particles and further between the particles and the sidewalls of the device body. The number of sub-volumes that will be formed in such a structure means that there will be a substantial volume of fluid within the device, despite the fluid being distributed amongst these relatively low volume sub-volumes or pockets, avoiding issues with low volumes of composition. Further, the interconnected nature of the sub-volumes will avoid difficulties with handling and useability. Providing and removing the composition from the device is straightforward, since separate removal from individual sub-volumes is not required. For example, where the composition is a fluid composition, this can allow a syringe to be inserted into only one part of the device and the avoidance of specialist equipment. This is particularly so where the particles are moveable relative to one another, since these can easily be manipulated to recover composition from the device.

[0044] As set out for the insert array, the use of a structural insert array also allows for a reduction or elimination of those existing methods for reducing radiolysis which themselves can have drawbacks, in the same way as the other aspects of the disclosure. For example, it provides a way of reducing radiolysis which can avoid the need to alter the composition itself, making manufacture easier and regulatory approval obsolete or easier. There is also more freedom in design. The use of particles of this size arranged in a stack allows for a vast arrange of device sizes, shapes and configurations, permitting incorporation into existing processes and techniques. This can avoid redesign manufacturing equipment or processes and handling equipment or processes.

[0045] In a fourth aspect, there is provided a use of a device of the third aspect to receive a composition comprising a radioisotope. The device may be in accordance with any of the aspects set out herein and the use (which may be a method of using the device to receive and hold a composition) have the same advantages and uses as set out above for the second aspect.Insert array

[0046] As set out above for the first and second aspects, the insert array is a provided within the interior chamber of the device body and comprises a one or more insert walls. An insert array as disclosed herein may also further be present in the devices of the other aspects, including the third and fourth aspects, in combination with the particles.Insert array form

[0047] In the aspects comprising an insert array, the insert array is a provided within the interior chamber of the device body and comprises one or more insert walls.

[0048] The device may comprise a plurality of internal sub-volumes defined by the one or more insert walls. For example, the insert array may comprise a plurality of insert walls and the device may comprise a plurality of internal sub-volumes, wherein each of the plurality of internal sub-volumes is defined by a corresponding one of the plurality of insert walls. The insert array may comprise a plurality of discrete inserts, each insert comprising at least one of the plurality of insert walls. In other words, the insert array may be an arrangement of separate inserts within the device body, each comprising one of the insert walls. Alternatively, it may be an arrangement of discrete sub-assemblies where each sub-assembly comprises plural insert walls. Assembly of these discrete inserts or sub-assemblies within the interior chamber of the device achieves the benefits set out above. The use of a plurality of discrete inserts or subassemblies provides for a flexible design which allows for modification of the insert array structure, for example depending on the specific use case (for example, different radioisotopes may use difference numbers of inserts to provide different sizes of sub-volumes), or which can allow for optimal utilisation of the space within the interior chamber. This can also enable removal and replacement of individual inserts as needed. For example, where there is a need to access the solution without being impeded by the inserts, a subset of these can be temporarily removed without a significant impact on overall radiolysis rate during the temporary removal. Alternatively, the insert array may be a unitary assembly comprising the plurality of insert walls. In other words, the insert array may be a single unitary or monolithic component itself comprising the plurality of insert walls connected or fused to one another. This can simplify manufacture and installation. The insert array itself may be connected to the device body(whether releasably so, or integrally formed with the device body) or may be removeable from the device body.

[0049] In configurations where there are discrete inserts or sub-assemblies, these may be spaced apart or in contact with one another. These may have a fixed relationship to one another (e.g. by bonding or fusing or through the use of connectors or spacers or other means) or may be moveable relative to one another within the confines of the device interior chamber. Where the inserts or sub-assemblies are moveable relative to one another, the size of the external subvolumes may be changeable but the insert (e.g. the shape, size, spacing features) can ensure that external sub-volumes are defined between the respective inserts.

[0050] Where there are discrete inserts, each insert may comprise an insert body comprising the insert wall and the wall may have an internal surface and an external surface. The internal sub-volume is accordingly delimited at least in part by the corresponding insert body. The insert body may enclose, either partially or fully, the internal sub-volume, for example providing a wall or sidewall which extends around the internal sub-volume. The insert body may additionally comprise other walls, such as a base and a top, which may further delimit the internal sub-volume.

[0051] Where present, an insert (where there is a single insert) or each (where there are plural) insert may comprise an insert body comprising a respective insert wall and the insert wall and / or insert body may define a tubular structure. This tubular structure has a hollow providing the internal sub-volume. The tubular structure may have a hollow cylindrical shape or a hollow prism shape. The tubular structure may be an elongate tubular structure, such as an elongate hollow cylindrical shape or a hollow prism shape. The tubular structure may have at least one open end, for example to provide fluid communication with at least some of the other internal and external sub-volumes, or these may be closed (e.g. using a removable cap).

[0052] Where there is a plurality of inserts, each may be arranged within the interior chamber of the device in contact (i.e. with the insert body or insert wall in contact) with an adjacent insert of the plurality of inserts, with the shape of each insert body causing the respective insert to be spaced apart from at least one of the other inserts of the plurality of inserts so as to provide the a further sub-volume therebetween. This advantageously creates a further type of subvolume enclosed between the insert walls of the different inserts, which further creates regions with smaller dimensions in which radiolysis is reduced. For example, for discrete inserts, the insert body may comprise a tubular structure and the plurality of inserts may be an arranged within the interior chamber with the tubular structure in contact with the tubular structure of an adjacent insert causing the respective inserts to be spaced apart from at least one of the other inserts of the plurality of inserts so as to provide an inter-insert sub-volume therebetween.

[0053] Such arrangements and shapes advantageously provides the plurality of different subvolumes, including the using the shape of the insert walls and insert body and, therefore, in an efficient and straightforward manner. Moreover, reliance on the shape of the insert assemblies to create the external and inter-insert sub-volumes enables the provision of small diameter inter-insert and external sub-volumes and further sub-volumes with narrow sections where the insert walls and internal surfaces of the device body meet. This creates regions where there is a high proportion of emitted particles being deposited into the insert walls and outside of the device. For example, insert walls with an arcuate shape (e.g. cylindrical or spherical shapes) packed together create external sub-volumes by virtue of forming spaced-apart pockets where tight packing is not possible. These shapes also taper from very narrow dimensions where the arcuate walls meet creating small regions. Thes regions have low radiolysis rates, but still feed into the central part of the inter-insert and external sub-volumes, maintaining efficient fluid transfer between the sub-volumes . The same can also be true of other shapes, including prism and polyhedron shapes, where these are packed or arranged in such a way that these inter-insert and external sub-volumes are created therebetween. Reliance on the shape also helps to provide efficient packing and use, avoiding further attachments or spacers, and allowing for easier manufacture and assembly.

[0054] Where the insert array is a single unitary component comprising a plurality of insert walls, the insert walls may be connected as a unitary structure but each at least partially defining a separate internal sub-volume, for example such that there are a plurality of internal subvolumes. Each insert wall may enclose an internal sub-volume, for example providing a wall or sidewall which extends around the internal sub-volume to separate it from the volume of composition between the sidewalls of the device body and the internal sub-volume. There may additionally be other walls, such as a base and a top, which may further delimit the internal sub-volume(s). Provision of single unitary component can be easier to install than separate inserts or sub-assemblies and further in that the shapes of the external sub-volumes are more fixed. The unitary assembly may also provide improved structural integrity and stability within the device as compared to separate inserts.

[0055] Where the insert array comprises a plurality of sub-assemblies joined together, each subassembly may comprise a plurality of the insert walls. The insert walls in each sub-assembly may be connected as a unitary structure but each at least partially defining a separate internal sub-volume, for example such that there are a plurality of internal sub-volumes. The subassemblies may combine to define an internal sub-volume(s). Each sub-assembly insert array may comprise an array body comprising the plurality of insert walls. The internal subvolume^) are delimited at least in part by the internal surface of the respective array body.Each insert wall may enclose an internal sub-volume, for example providing a wall or sidewall which extends around the internal sub-volume. There may additionally be other walls, such as a base and a top, which may further delimit the internal sub-volume(s).Insert wall structure

[0056] By “delimit” or “define” a sub-volume, it is meant that the respective surface (or the wall defining the respective surface) at least partially encloses and separates a volume from the other sub-volumes and the remainder of the interior chamber of the device body. This means that the surface or wall acts as a boundary or partition that creates a distinct area inside the device. This may be enclosing (which means to surround at least a majority of a portion of the interior chamber to form the sub-volume but still have an interconnection to allow for some fluid communication, e.g. through opening(s) through the insert wall) or fully enclosing the sub-volume so that it is completely separated (this may be a temporary arrangement, with a closeable aperture for fluid communication, for example). In some embodiments, each insert wall may enclose a separate internal sub-volume. Partially enclosing may include fully enclosing in at least one dimension while remaining open in another, such as in the form of a tubular structure open at least one end. Thus, the term “enclose” encompasses configurations in which a wall completely surrounds a volume in all dimensions and those in which the enclosure is directional or partial. The wall may not need to be a fluid impermeable barrier, but may in some embodiments.

[0057] By “at least partially delimiting” or “at least partially defining” it is meant that the insert wall defines a part of the enclosure either entirely or together with additional walls, such as other insert walls or the walls of the device (sidewall, base, etc.). That is, the insert wall may co-operate or connect (e.g. by being placed against) further walls or surfaces to provide the sub-volume in question. For example, combining with another internal or external surface to define the respective sub-volume. For example, the internal surface may combine with the internal surfaces of other insert walls to define the internal sub -volume or the external surface may combine with the external surface of another insert wall of the device body walls.

[0058] The one or more insert walls and device body wall(s) (e.g. sidewall) can be any shape for creating the sub-volumes within the device. The insert wall(s) may be planar (e.g. extending straight across a section of the interior chamber) or may be curved or be formed of varying parts across the surfaces. The internal and external surfaces of the insert wall(s) may be different shapes (i.e. the insert walls may be non-uniform across their thickness). The insert wall(s) may have an arcuate shape (e.g. cylindrical or spherical shapes) so that, when packed together, the insert walls create external sub -volumes by virtue of forming spaced-apart pocketscaused by the arcuate shape. The use of arcuate insert walls, and particularly arcuate walls having a convex external surface, advantageously creates external sub -volumes with shapes which taper from very narrow dimensions where the arcuate walls meet (dependent on the arcuate shape) to larger central portions of the sub-volumes. This creates small regions with very low radiolysis rates, but which still feed into the central part of the external sub-volume, where fluid transfer is easier. The same is also true of other shapes, including prism and polyhedron shapes to extent where these are packed in such a way that these external sub-volumes are created therebetween. Similarly, the device body sidewall(s) may additionally or alternatively have an arcuate shape (e.g. cylindrical or spherical shapes).

[0059] The or each insert wall may delimit or define an insert chamber, the insert chamber delimiting or defining the internal sub-volume. In other words, where there are plural insert walls, each insert wall may define or enclose its own internal sub-volume such that the internal surface of the particular wall defines the internal sub-volume. The wall defining the internal surface may partially or fully enclose the sub-volume. The wall defining the chamber may provide a tubular structure having a hollow providing the internal sub-volume. The tubular structure may be an elongate tubular structure and may be a hollow cylindrical shape or a hollow prism shape, such as an elongate hollow cylindrical shape or a hollow prism shape. The tubular structure may have at least one open end, for example to provide fluid communication with at least some of the other sub-volumes, or these may be closed (e.g. using a removable cap). In such embodiments, the internal sub-volumes may be those fully enclosed by each insert wall and the external sub-volumes may be those defined in conjunction with other parts of the device, namely other insert walls and / or the device body.

[0060] The wall thickness of the or each of the insert walls may be at least 50 pm, such as at least 100 pm, such as at least 250 pm. This can be from 50 pm to 2mm, such as from 100 pm to 2mm or from 100 pm to 1mm. These thicknesses, particularly of materials such as glasses, plastics, metals and ceramics, will prevent transfer of a significant proportion, if not all, of the emitted particles from the respective sub-volume to related portions of the interior chamber, thereby reducing radiolysis.Internal, inter-insert and external sub-volumes

[0061] A cross-section dimension of the internal and / or inter-insert sub-volume(s) may be related to the range of the emitted particles (e.g. at least one of (i) the beta (beta(+) or beta(-)) range of the radioisotope or (ii) the alpha range of the radioisotope). It will be appreciated that the emitted particle type depends on the isotope in question, as does the path length. Table 1 provides examples of average (mean) and maximum ranges for the primary emitted particles from a number of radionuclides.

[0062] A cross-section dimension of the internal and / or inter-insert sub-volume(s) may be less than or equal to 3 x average (mean) range of an emitted particle. The range may be range within water, as set out in Table 1, below. Accordingly, for each isotope in Table 1, a device used forthat composition may have a cross-section dimension of the internal and / or inter-insert sub-volume(s) may be less than or equal to 3 x average (mean) range of an emitted particle as set out in Table 1. Although it will be appreciated that range may vary within different mediums, average range in water provides a good model and devices adhering to this will provide the increased attenuation and reduced probability of depositing of emissions, discussed above. This limitation may further be all cross-sectional dimensions in a single plane. For example, this may be a maximum cross-section dimension and it may be along a whole length of the insert or sub-volume, for example.

[0063] Alternatively, for each isotope in Table 1, a device used for that composition may have a cross-section dimension of the internal and / or inter-insert sub-volume(s) which is be less than or equal to the values set out in the column “Optional internal sub-volume, inter-insert subvolume and / or external sub-volume maximum dimensions (mm)”.

[0064] A cross-section dimension of the internal and / or inter-insert sub-volume(s) may be below at least one of (i) the beta (beta(+) or beta(-)) range of the radioisotope or (ii) the alpha range of the radioisotope. Additionally or alternatively, a cross-section dimension of the external sub-volume(s) may be below at least one of (i) the beta (beta(+) or beta(-)) range of the radioisotope or (ii) the alpha range of the radioisotope. Prevention of any of alpha or beta particles interacting with the composition will reduce radiolysis and selecting a diameter which is less than at least the beta particle ranges for a particular radioisotope will significantly increase the likelihood that the emitted particles will enter the insert walls rather than interact with other components in the composition. Further, [3-, P+ or a- emissions and those radioisotopes emitting these are thought to benefit the most from the geometric restrictions.

[0065] This can further be all cross-sectional dimensions in a single plane, such that all dimensions in that plane are less than or equal to at least one of (i) the beta(+) or beta(-) range of the radioisotope or (ii) the alpha range of the radioisotope. This can be a maximum range or an average (mean) range, as set out in Table 1, below. The range can be the range of the emitted particles in water.

[0066] References herein to a single plane can be, for example, where the insert wall provides an enclosure surrounding the internal sub-volume, such as a cylinder or a prism-shape, but may permit a longer dimension in other directions, such as perpendicular to the plane in question. For example, where the insert wall or the internal surface thereof has a cylindrical or prismshape, the cross-section dimensions may be in a plane perpendicular to the central elongate axis.

[0067] Cross-section dimensions as referred to herein refer to the distance between two surfaces defining the sub-volume. This may be a diameter, for example. The cross-section dimension may be a maximum cross-section dimension, such as the maximum diameter, in a particular plane. The plane may be perpendicular to the insert walls, which in the case of tubular bodies may be perpendicular to the central axis of the tubular bodies, which may be parallel to the base of the device body. This can further be all cross-sectional dimensions in a single plane. For example, where the dimension refers to the internal sub-volume, this can be measured between two opposing parts of the insert wall or the insert wall and another insert wall defining the internal sub-volume. Where the insert wall provides an enclosure surrounding the internal sub-volume, such as a cylinder or a prism-shape, this may be between two opposing surfaces of the insert wall (i.e. an internal diameter). It will be appreciated that a cross-sectional dimension may permit a longer dimension in other directions, such as perpendicular to the plane in question. For example, where the insert wall or the internal surface thereof has a cylindrical or prism shape, the cross-section dimensions (e.g. diameter) may be in a plane perpendicular to the central elongate axis. Where the dimension refers to an external subvolume, this similarly can be measured between two opposing parts of the insert wall, or the insert wall and another wall defining the external sub-volume. For an inter-insert sub-volume, this may be between the insert walls defining the sub-volume, for example, between the external surfaces of the insert walls defining the sub-volume.

[0068] The or each internal and / or inter-insert sub-volume (e.g. each insert chamber for the internal sub-volume) may have a maximum cross-sectional dimension, such as a diameter, of from 20 pm to 8 mm. This size ranges optimize the balance between reducing the volume between the walls (and hence radiation absorption), attenuation and the volume for composition containment. It has surprisingly found that significant radiolysis reduction can be obtained within this range without difficulties in handling caused by further reduction. For example, narrow sub-volumes can restrict fluid flow and often require specialist equipment to insert and remove composition therefrom. This can be problematic and increase complexity of handling. Without wishing to be bound by theory, it is thought that the dimensions disclosed herein also provide attenuation of the emitted particles which thereby reduces attenuation in the composition. This maximum cross-sectional dimension may be from 100 pm to 8 mm. For example, from 100 pm to 5 mm, from 500 pm to 5 mm, such as greater than 1 mm to 6 mm, or 1.5 mm to 6 mm, or 2 mm to 6 mm. These provide dimensions which are of the order of, but typically higher, than the average range of beta(+) emissions for many of the commonradioisotopes used in radiopharmaceuticals. This provides a reduction in radiolysis but still provides a larger volume for provision of a useful volume of fluid and of openings to facilitate use.

[0069] It will be appreciated that the specific maximum cross-sectional dimension used may be selected based on factors such as the type and activity of radioisotope, desired composition volume, and radiolysis reduction goals. Table 1 lists exemplary radioisotopes. The internal sub-volumes, and / or inter-insert sub-volumes and / or external sub-volumes may have the maximum dimensions listed therein when used with a composition comprising the radioisotope listed therein.Table 1 (* includes alpha emitting daughter nuclides)

[0070] An external sub-volume is defined within the interior chamber between the external surface of the one or more insert walls and at least one internal surface of the device body (e.g. the internal wall of the sidewall) and may further be between insert walls. For example, between an external surface of an insert wall and an external surface of another insert wall. There may be plural external sub-volumes and, in such cases, there may be fluid communication between all of the external sub-volumes. The insert array - and the one or more insert walls - may therefore be arranged within the interior chamber so as to define a plurality of external sub-volumes within the interior chamber.

[0071] The external sub-volume may have a maximum dimension (e.g. maximum cross-sectional dimension), for example a maximum diameter. This may be a cross-sectional dimension in one dimension, such as perpendicular to the insert wall or perpendicular to a central axis defined by the sidewall(s) of the device body. The distance may be between the insert wall (e.g. the external surface delimiting the external sub-volume) and the internal surface of the device body delimiting the external sub-volume (e.g. the sidewall) or, where another insert wall also defines the external sub-volume, this may be between the insert walls if this provides the maximum dimension. This may be less than or equal to the diameter of the interior chamber of at least one of the respective inserts. The external sub-volume may have a maximum cross-sectional dimension, such as a diameter, of from 20 pm to 8 mm. This may be from 100 pm to 8 mm. For example, from 100 pm to 5 mm or from 500 pm to 5 mm, such as greater than 1 mm to 6 mm, or 1.5 mm to 6 mm, or 2 mm to 6 mm. The external sub-volume may have a maximum dimension as measured between the external surface and the at least one sidewall of the device body and an external surface of one of the other of the plurality of insert walls of less than or equal to the diameter of the interior chamber of at least one of the respective insert walls (e.g. the inserts, where discrete), for example the interior chamber defined by theinsert wall at least partially forming the external sub-volume in question. The maximum crosssection dimension of the external sub-volume(s) may be related to the range of the emitted particles. For example, it may be less than or equal to 3 x average (mean) range of an emitted particle, as defined in Table 1.

[0072] The internal sub-volume(s) defined by the insert walls may (each) have a volume of at least 0.01m, such as at least 0. ImL or at least ImL, for example from 0.01 mL to lOmL, such as from 0. ImL to 8mL, 0.5mL to 8mL, from 0.1 mL to 5mL, from 0. ImL to 2mL. The interinsert sub-volume(s) defined by the insert walls may (each) have a volume of at least 0.01m, such as at least 0. ImL or at least ImL, for example from 0.01 mL to lOmL, such as from 0. ImL to 8mL, 0.5mL to 8mL, from 0.1 mL to 5mL, from 0. ImL to 2mL. The external sub-volume(s) may (each) have a volume of at least 0. ImL, such as at least ImL, for example from 0.1 mL to lOmL, such as from O.lmL to 8mL, 0.5mL to 8mL, from 0.1 mL to 5mL, from O.lmL to 2mL. The volumes of the sub-volumes is defined by the walls which define the respective volume. Where there is a disconnect in the walls, such as an opening or a gap defined by a neck portion before opening up into a wider portion, the sub-volume is delimited by a straight-line between the walls defining the disconnect. For example, in the case of a tubular structure with openings at either end, the top of the sidewall(s) defining the tubular structure may delimit the top and the bottom of the volume.

[0073] At least one of the external sub-volumes may have a volume that is less than the volume of the internal sub-volume and / or a cross-sectional area of at least one external sub-volume may be smaller than that of the internal sub-volume. In this way, the external sub-volume may reduce radiolysis to a greater extent as compared to the internal sub-volume.

[0074] Each sub-volume may be in fluid communication with the other sub-volumes. For example, the internal, inter-insert and external sub-volumes may all be in fluid communication. Where the composition is a fluid composition, such as a solution or a flowable solid, this may be so that the solution can flow between the at least one internal sub -volume and the external sub-volume. This allows for easier composition handling, such as providing and removing the composition from the device, since removal from individual sub-volumes is not required. For example, this can allow for only one sub-volume to be large enough to receive a syringe for handling or injection into a patient (which sub-volume may have a higher radiolysis rate) and the remainder can be smaller volumes (which can then have reduced rates of radiolysis) but which are still in fluid communication with the larger volume sub -volume so as to permit straightforward removal. In the case of discrete inserts which are moveable relative to one another, in some cases it is sufficient that these can move to provide the fluid communication.In some cases, the fluid communication may be permanently in fluid communication after insertion of the insert array.

[0075] Although it has been set out that there are external and internal sub -volumes (and optionally inter-insert sub-volumes) within the interior chamber, it will be appreciated that there may be parts of the interior chamber which may be outside of these sub-volumes. For example, where the composition is provided at a height which is above the height of the insert array within the device body. This region can be referred to as an excess fluid region. This may be limited in size and volume to reduce the amount of fluid residing outside the confines of the external and internal sub-volumes (and inter-insert sub-volumes, where present), for example to a volume of less than 50% of the total volume of the composition within the device body, such as less than 25%, or less than 10%.

[0076] Although the insert array and the features thereof have been set out in respect of the first and second aspects, it will be appreciated that such an insert array may further be used in respect of the other aspects, including the device of the third and fourth aspects and the features disclosed in respect of these. In particular, the devices of the other aspects and the further embodiments disclosed in respect of these may further comprise an insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls, wherein the one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber; wherein at least one external sub-volume is formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the one or more device sidewalls; and wherein the device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes. The particles may, for example, be received within at least one of or each of the external sub-volumes, the internal sub-volumes and the inter-insert sub-volumes (where the latter is present).Particles

[0077] The devices of the third and fourth aspects include a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack (or “arrangement”) and define a plurality of fluidly connected sub-volumes between the plurality of particles within the interior chamber. Each particle has a maximum dimension of from 20 pm to 8 mm. The particles disclosed herein may also further be present in the devices of the other aspects, including the first and second aspects, in combination with the insert array.Particle geometryParticle size

[0078] Each particle has a maximum dimension (e.g. a maximum diameter) of from 20 pm to 8 mm. As discussed above, this size range provides optimal sub-volume size as well as shielding through the presence of the particles themselves. This also balances reducing radiolysis and the volume of the composition within the device. It has been found that difficulties in handling small volumes increase and lead to a falloff in useability. For example, narrow sub-volumes can restrict fluid flow and often require specialist equipment to insert and remove composition therefrom. This can be problematic and increase complexity of handling. Surprisingly, these sizes still provide an effective reduction in radiolysis. This maximum dimension may be from 100 pm to 8 mm. For example, from 100 pm to 5 mm, from 500 pm to 5 mm or from 1 mm to 6 mm (such as greater than 1 mm to 6 mm, or 1.5 mm to 6 mm, or 2 mm to 6 mm). These provide sub-volume dimensions which are of the order of, but typically higher, than the average range of beta(+) emissions for many of the common radioisotopes used in radiopharmaceuticals. This provides a reduction in radiolysis but still provides a larger volume for provision of a useful volume of fluid and of openings to facilitate use. It will be appreciated that this does not preclude particles of a larger diameter being present in the device provided there are a plurality within the stack as set out herein.

[0079] The particles may have a maximum dimension which is related to the range of the emitted particles, given that the diameter will in part define the size of the voids between the particles and, further, because the thickness of the particles will prevent through passage of emitted particles. For example, a maximum dimension may be less than or equal to 3 x average (mean) range of an emitted particle (but greater than the lower limit of 20 pm). The range may be range within water, as set out in Table 1, below. Accordingly, for each isotope in Table 1, a device used for that composition may have a maximum dimension of less than or equal to 3 x average (mean) range of an emitted particle as set out in Table 1. Additionally or alternatively, the particles may be sized and shaped so that the average (mean) of the average (mean) cross-sectional dimension of the sub-volumes defined therebetween is less than or equal to 3 x average (mean) range of an emitted particle, as defined in Table 1. This may be determined and further defined in line with the internal or inter-insert sub-volume definitions as set out for the insert array.

[0080] The maximum dimension refers to the largest dimension of (e.g. across) the particle. For spherical particles, this would be the diameter. For non-spherical particles, the maximum dimension may be measured as the longest dimension across the particle. The maximum dimension may be determined using techniques such as optical microscopy, electronmicroscopy, or particle size analysers. For irregularly shaped particles, multiple measurements can be taken to determine the maximum dimension.

[0081] The particles of the stack may have an average particle size, for example a mean particle size, of from 20 pm to 6 mm, such as from 100 pm to 5 mm or from 500 pm to 5 mm (such as greater than 1 mm to 6 mm, or 1.5 mm to 6 mm, or 2 mm to 6 mm). Mean particle size may be measured as the mean diameter of a representative sample of particles. The particle size distribution can be determined using techniques such as dynamic light scattering, laser diffraction, or image analysis of microscopy data. The arithmetic mean of the measured diameters may then be calculated to determine the average particle size. A more uniform spread of particle sizes may lead to a more uniform reduction in radiolysis between devices and regions of composition.Particle form

[0082] The particles may be of any shape and the stack (or “arrangement”) may comprise particles of different shapes. The particles may be spheres, polyhedrons, rods, hollow cylinders, or discs, for example. The particles may each comprise at least one rounded or arcuate surface. Particles with rounded or arcuate surfaces (e.g. cylindrical or spherical shapes) have been found to pack together to create sub-volumes having desirable shapes. These shapes of the sub-volumes formed taper from very narrow dimensions where the arcuate walls meet, particularly where the arcuate walls diverge and taper away from one another, creating small regions with small dimensions and diameters. This create regions with low radiolysis rates, but which still feed into the central part of each sub-volume, where fluid transfer is easier. These can also avoid close packing of the beads to ensure that there are ample sub-volumes. Each particle of the stack may have a shape selected from substantially spherical, substantially spheroidal, substantially ellipsoidal, substantially ovoidal, substantially toroidal, or substantially cylindrical. This can be spherical, spheroidal, ellipsoidal, ovoidal, toroidal, or cylindrical.Stack

[0083] By “stack” or “arrangement”, it is meant an arrangement of a plurality of particles, where the particles are each in contact with other particles within the stack or arrangement. The stack can include particles arranged randomly, for example as a pile, or in a predefined structure. The particles may be interconnected so as to prevent relative movement or may be moveable relative to one another.

[0084] The particles in the stack form a plurality of fluidly connected sub-volumes therebetween. These can be considered to be equivalent to the inter-insert sub-volumesdiscussed in respect of the insert array and have the same benefits as these and the internal subvolumes. The particles in the stack may further define sub-volumes equivalent to the external sub-volumes between either a particle and the device body (i.e. an internal surface thereof, such as the sidewall of the device body) or plural particles and the device body.

[0085] The stack includes a plurality of particles, such as at least 5 particles, at least 10 particles or at least 20 particles, at least 100 particles. These can be discrete particles or may be connected, such as fused or bonded. This can be, for example, after insertion into the device.

[0086] The use of particles creates a network of small sub-volumes, effectively limiting the interaction between radiation and the composition while maintaining fluid connectivity. The sub-volumes may each have a maximum cross-sectional dimension, for example a maximum diameter, as measured between the external surface of the particle delimiting the sub-volume and the internal surface of the part of the device body (e.g. sidewall) and / or an external surface of one of the other particles of from 20 pm to 8 mm. This maximum cross-sectional dimension may be from 100 pm to 8 mm. For example, from 100 pm to 5 mm or from 500 pm to 5 mm, such as greater than 1 mm to 6 mm, or 1.5 mm to 6 mm, or 2 mm to 6 mm. The sub-volumes may each have a maximum dimension as set out above of less than or equal to the diameter of the particle(s) delimiting or defining the sub-volume. In some cases, the cross-section dimension of the internal sub-volumes formed by the beads may be less than or equal to below at least one of (i) the beta(+) or beta(-) range of the radioisotope or (ii) the alpha range of the radioisotope. This configuration can help to ensure that the emitted particles deposit in the walls of the beads or the device, not the composition, thereby reducing radiolysis.

[0087] The sub-volume(s) defined by the particles may (each) have a volume of at least O.OlmL, such as at least 0. ImL, for example from 0.1 mL to lOmL, such as from 0. ImL to 8mL, 0.5mL to 8mL, from 0.1 mL to 5mL, from O.lmL to 2mL. The external sub-volume(s) may (each) have a volume of at least 0. ImL, such as at least ImL, for example from 0.1 mL to lOmL, such as from 0. ImL to 8mL, 0.5mL to 8mL, from 0.1 mL to 5mL, from 0. ImL to 2mL. The volumes of the sub-volumes is defined by the walls which define the respective volume. Where there is a disconnect in the walls, such as an opening or a gap, the sub -volume is delimited by a straight-line between the walls defining the disconnect at the disconnection. For example, in the case of a tubular structure with openings at either end, the top of the sidewall(s) defining the tubular structure may delimit the top and the bottom of the volume.

[0088] A plurality of the sub-volumes are in fluid communication. It is conceivable that some sub-volumes will be fluidly isolated at least in some configurations, but in some cases all of the sub-volumes are either in fluid communication or can be manipulated or moved into fluid communication. By “delimit” or “define” a sub-volume, it is meant that the respective surfaceof the particles surrounding the volume at least partially encloses and separate a volume from the other sub-volumes and the remainder of the interior chamber of the device body. This means that the surface or wall acts as a boundary or partition that creates a distinct area inside the device. This may be enclosing (which allows for some fluid communication through opening(s)).

[0089] At least one of the plurality of particles is movable relative to another of the plurality of particles. Each of the particles within the stack may be relative moveable to the other particles. This can be advantageous as it provides for easy access to the sub-volumes, for example through manipulation of the particles.Device Body

[0090] The device body as set out for any of the aspects disclosed herein comprises one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface. The interior chamber may comprise at least one opening, which may be defined by the sidewall(s). The device body may further comprise a base from which the sidewall(s) extends and providing a further delimitation of the interior chamber. Accordingly, the interior chamber is delimited at least in part by the at least one sidewall and, where present, the base. The composition is received within the interior chamber.

[0091] The device may be any device in which a composition comprising a radioisotope may be held or stored. For example, the device may be a vial or container for holding a composition comprising a radioisotope. Such a vial may further comprise an opening defined by the top of the sidewall(s) and a removeable cap to close the opening. Alternatively, the device may be or form a part of a separation apparatus, such as a filter or column, or other vessel used during synthesis or purification of radioisotope compositions. The device may also be a reaction vessel, such as a microreactor. Where a filter or a column, such as cylindrical column or vessel, the base may be a part of the cylindrical walls (the lowermost portion) and hence be integral with the sidewalls.Materials

[0092] The device body may comprise or be formed of any suitable material, for example, selected from at least one of a glass, a glass-ceramic, a ceramic, a polymer or a metal (including a metal compound or allow, such as a metal oxide). Examples of suitable polymers include the polymeric materials may include one or more fluoropolymers (such as polyvinylidene fluoride (PVDF) or ethylene tetrafluoroethylene (ETFE)), polyolefins (such as high-density polyethylene (HDPE), cyclic olefin polymers or polytetrafluoroethylene (PTFE)) or others,such as silicone or butyl rubber. The device body may further comprise a coating, for example on its inner surface (i.e. the portion of the walls defining the interior chamber), and / or the device walls (e.g. at least the inner surface) may be modified to enhance their effectiveness in reducing radiolysis. For instance, the surfaces may be coated with a coating, such as a polymeric coating, provided on at least the inner surface. Where this is a polymeric coating, this may be the same polymer(s) as those listed above.

[0093] Where particles are present, each of the plurality of particles may comprise or be formed of any suitable material, for example, comprise or consist of a glass, a glass-ceramic, a ceramic, a polymer or a metal. This may include metal compounds or alloys, including metal oxides. Examples of suitable polymers include cyclic olefin polymers, high-density polyethylene (HDPE), or polytetrafluoroethylene (PTFE). The particles may be modified to enhance their effectiveness in reducing radiolysis. For instance, the surfaces may be coated with a coatings. Each of the plurality of particles may therefore comprise a core and a coating surrounding the core. For example, a core comprising or consisting of a glass, a glass-ceramic, a ceramic or a polymer.

[0094] Where an insert array is present, the insert array may comprise or be formed of any suitable material, for example, selected from at least one of a glass, a glass-ceramic, a ceramic, a polymer or a metal (including a metal compound or alloy, such as a metal oxide). Examples of suitable polymers include the polymeric materials may include one or more fluoropolymers (such as polyvinylidene fluoride (PVDF) or ethylene tetrafluoroethylene (ETFE)), polyolefins (such as high-density polyethylene (HDPE), cyclic olefin polymers or polytetrafluoroethylene (PTFE)) or others, such as silicone or butyl rubber. Alternatively, this may be formed from a mineral, such as apatite, calcite, or bentonite. The insert array may further comprise a coating. The insert wall(s) may be modified to enhance their effectiveness in reducing radiolysis. For instance, the surfaces may be coated with a coating, such as a polymeric coating, provided on at least the internal surface and / or external surface. Where this is a polymeric coating, this may be the same as those listed above for the insert array.

[0095] In embodiments comprising an insert array, the portion of the walls of the device body (including the base) defining the interior chamber may have a combined surface concentration of SiOH and SiO- moieties of less than 4 nm-2 and the surfaces of the insert array (including at least the internal surface and external surface) may further comprise a surface concentration of SiOH and SiO- moieties of less than 4 nm-2. In embodiments comprising a plurality of particles, the portion of the walls of the device body (including the base) defining the interior chamber may have a combined surface concentration of SiOH and SiO- moieties of less than 4 nm-2 and the surfaces of the particles may further comprise a surface concentration of SiOHand SiO- moieties of less than 4 nm-2. This may be less than 2 nm-2. It has been discovered that degradation of radiopharmaceutical components, such as a radioisotope binding species (which may be a chelating agent, such as one comprising a peptide portion and a chelator portion), may occur in the presence of glass or glass-ceramics and be catalyzed by SiO-. This is particularly so in the presence of at least one stabilizer (such as a phenolic acid or salt thereof and / or ascorbic acid or a salt thereof). By having fewer SiOH or SiO- moieties at the surface, this is reduced. The surface concentration of SiOH / SiO- groups can be measured as known in the art. This may be measured using XPS (X-ray photoelectron spectroscopy) to measure the number of silanol or siloxide groups. Such a measurement method comprises irradiating a portion of the sample and fitting the curve of the resultant spectra in order to determine the presence of SiOH and SiO- groups. A typical O ls peak-fitting approach may be used to characterize the oxygen speciation or a stoichiometry-based algorithm via elemental composition may be used as described in Banerjee et al., Effect of heat treatment on the surface chemical structure of glass: Oxygen speciation from in situ XPS analysis, Journal of the American Ceramic Society, Volume 101, 2018, 644-656, DOI: 10.1111 / j ace.15245. SiOH quantification may be carried out after dehydration of the material, such as by heating to temperatures in excess of 175°C (e.g. where uncoated glass or glass-ceramic) or exposure to a desiccant. Numerous areas of the inner surface material may be sampled, such two different areas or three different areas, in order to obtain a mean concentration of SiOH and SiO- groups, which is then taken as the concentration for the material in question. These areas may be of any suitable size, such as 100 pm x 100 pm. The areas should be spaced sufficiently far apart such that previous X-ray irradiation does not affect the result, such as being spaced 1 mm apart. The surface concentration of SiOH / SiO- on the inner surface or particles may be measured prior to filling the device with the solution. Alternatively, the surface concentration of SiOH / SiO- on the inner surface or particles may be measured after having contacted the inner surface with the solution for at least 1 minute, wherein the solution has then been removed to enable the measurement and without having further treated the surface.

[0096] Providing an inner surface which is substantially free of SiOH and SiO- can be achieved in a number of ways. The inner surface of the device body may be formed from a material which does not comprise SiOH or SiO- moieties on the surface. This may be that the device body or defining the inner surface is formed from or comprises an alternative material, i.e. one which does not comprise SiOH or SiO- moieties (e.g. has a concentration of less than 0.1 mol% SiOH, such as less than 0.05 mol% SiOH). Or this may be that a coating is provided on the device body (as an inner wall portion), which coating is formed from or comprises an alternative material, i.e. one which does not comprise SiOH or SiO- moieties. Alternatively oradditionally, the inner surface (e.g. the inner wall portion defining the inner surface) may have been treated to remove SiOH and SiO- moieties. For instance, the inner surface may be made of a glass or glass ceramic which has been treated to remove SiOH and SiO- moieties. Alternatively or additionally, this can be achieved through the selection of a materials for these parts or a coating over these parts. For example, the device body may be formed from or comprise a polymer or metal. Similarly, the insert array or the particles may be formed from or comprise a polymer or metal. Where a polymer, the polymer may be selected from one or more of a fluoropolymers (such as poly vinylidene fluoride (PVDF) or ethylene tetrafluoroethylene (ETFE)), a polyolefin (such as high-density polyethylene (HDPE), a cyclic olefin polymer or polytetrafluoroethylene (PTFE)) or butyl rubber.Composition

[0097] The devices as set out for any of the aspects and embodiments disclosed herein can comprise a composition comprising a radioisotope. This may be a composition comprising a radiopharmaceutical or a radiopharmaceutical composition. A radiopharmaceutical is a drug or composition which includes a radioisotope, such as a compound labelled with or chelating a radioactive isotope. These are for in medical applications, including diagnostic imaging and therapeutic treatments. The composition may be a fluid composition. A fluid composition is a flowable composition. This may be a gas, a solution or a flowable solid, such as a powder. Where the composition is a solid, this may include radioisotopes deposited on solids, such as on powders.

[0098] The devices as set out for any of the aspects and embodiments disclosed herein can comprise a solution comprising a radioisotope. Where the device comprises a solution, the solution may have a radioactive concentration of at least 0.01 mCi / mL (0.37 MBq), at least 0.1 mCi / mL (3.7 MBq), or at least ImCi / mL (37 MBq). This may be up to 1000 mCi / mL (37000 MBq). Radiolysis is not linearly proportional to radioactivity concentration at higher concentrations, and increases significantly at a threshold concentration, where afterwards there is essentially an exponential increase. It has been found that the devices disclosed herein can increase this threshold concentration before. That is, the concentration threshold at which radiolysis increases significantly can be itself be increased. For example, by at least 50%. Accordingly, the devices allow for an increased radioactive concentration. Accordingly, the solution may have a radioactive concentration of at least 50 mCi / mL (1850 MBq), at least 100 mCi / mL (3700 MBq). The solutions may be aqueous solutions. Where this is a solid, there may be at least Ing of a radioisotope, such as at least lOng, at least 50ng, at least O.lmg or atleast Img. The solid may have an activity of at least 1 MBq, such as at least 10 MBq, at least 100 MBq or at least 1 GBq.

[0099] The compositions comprise a radioisotope. A radioisotope may form part of a radiolabelled-compound, which can be a radiolabelled-pharmaceutical. For example, the compositions (e.g. solutions) may comprise a radioisotope bound to a targeting moiety. The radioisotope can be bound to the targeting moiety directly either via a covalent bond (such as C-C, O-C, C-F etc), ionic bond (e.g. Si-F) adhesion / adsorption to nanoparticles or via complexation to a radioisotope binding species, such as an organic molecule, a peptide, a protein, a microparticle or a nanoparticle (e.g. a chelator / ligand or complexing agent). Examples of complexing agents are crown ethers (15-Crown-5, 18-Crown-6 etc), nitrogen and / or oxygen containing macrocycles or open chains (e.g. DOTA, DTP A, EDTA, DOTAM, DO3A, NOTA, NODA, N02A, PCTA, Macropa, DFO, DFO*, DO3A, PCTA, TCMC, NOD AGA, HEHA). The complexing agents holding the radioisotope is bound / connected to a targeting moiety / targeting vector (small molecule, peptide, protein, antibody, affibody, nanoparticle etc), either directly or via a linker such as a PEG linker. Where the composition comprises a radiolabelled compound, radiolysis may cause degradation of the whole radiolabelled compound as well as interaction with the other components of the composition.

[0100] The radioisotopes may be selected from carbon-11, nitrogen-13, fluorine-18, sodium-24, phosphorous-32, scandium-47, cobalt-58, zinc-62, copper-62, copper-64, copper-67, gallium-68, bromine-76, bromine-77, bromine-82, rubidium-86, zirconium-89, strontium-89, yttrium-90, yttrium-91, palladium- 103, palladium- 109, Indium-Ill, indium-114m, tin-117m, iodine-121, iodine-123, iodine-125, iodine-131, terbium-149, terbium-152, samarium-153, terbium-161, holmium-161, holmium-166, erbium-169, lutetium-177, rhenium-186, rhenium-188, gold-198, astatine-211, bismuth-211, lead-212, bismuth-212, bismuth-213, radium-223, radium-224, actinium -225, and thorium -227.

[0101] The composition may comprise further components, such as diluents, buffers, a pharmaceutically acceptable salt, radiostabilizers, drug excipients, or reagents and precursors. For example, there may be a buffer solution (HO Ac, NaOAc, NH4OAc, HEPES, carbonates, phosphates), radiostabilizers (e.g. gentisic acid, ascorbic acid, methionine, ethanol, glutathione) and / or saline. These may be subject to degradation by the emitted particles.

[0102] The composition may comprise a matrix, such as a solvent or carrier, in which the radioisotope is provided. In some cases, the matrix may be subject to degradation by the emitted particles. Where this is a solution, the matrix is typically water based on ethanolic water based.Other Definitions

[0103] The sub-volumes as used herein for all aspects, including the internal, inter-insert and external sub-volumes, may be regions which are surrounded partially or in entirely in at least one dimension or plane by a wall or combination of walls. As used herein, the term "subvolume" may refer to a portion of the larger interior chamber volume that is at least partially separated or partitioned to create a distinct smaller volume of fluid. A sub-volume may be partially enclosed or defined by physical structures such as walls, inserts, or particles. In certain implementations, sub-volumes may remain in fluid communication with the larger volume through openings or gaps. Sub-volumes may be fully enclosed in at least one plane or dimension whilst remaining being open in others.Specific implementations

[0104] Figs. 1A and IB provide a schematic depiction of a device 100 in the form of a device lOOfor receiving a solution 105 comprising a radioisotope, the device 100 comprising a device body 110 and an insert array 150 and a solution 105 provided in the device body 110.

[0105] The device body 110 has a cylindrical shape with a circular base 118 and a cylindrical sidewall 115 extending upwards from the base 118 around the perimeter of the base 118. The sidewall 115 and base 118 enclose an interior chamber 120 for receiving the solution 105. An opening 116 is provided at the top of the device 100 and is defined by the top of the sidewall 115. The solution 105 can be provided to and removed from the interior chamber 120 of the device 100 through the opening 116. A cap (not shown) can be used to close the opening 116 and thereby seal the interior chamber 120 of the device 100.

[0106] The insert array 150 is provided within the interior chamber 120 of the device body 110. The insert array 150 comprises a plurality of discrete inserts 160 in the form of identical hollow elongate cylindrical inserts 160, with the cylindrical wall of the inserts 160 forming the insert wall 165 of each insert 160. The hollow cylindrical shape is open at both end faces, providing a top opening 161 and a bottom opening (not labelled) at either end and providing fluid communication (allowing fluid flow) between the interior hollow portion of each insert 160 and the interior chamber 120 of the device body 110. The inserts 160 are each arranged upright within the device body 110 and extend along the majority of the height of the device 100. The inserts 160 are arranged parallel to (i.e. coaxial with) one another and the sidewall 115 of the device body 110 and in contact (i.e. abutting) neighbouring inserts 160. The inserts located adjacent to the edge of the device body 110 also contact the sidewall 115 of the device body 110.

[0107] As most clearly visible in the top-down view of Fig. IB, this arrangement creates a series of internal sub-volumes 170, inter-insert sub-volumes 172 and external sub-volumes 175 within the interior chamber 120. The hollow void within the cylindrical inserts 160 and surrounded around its circumference in the plane parallel to the base 118 by the internal surface of the insert wall 165 provides an enclosed internal sub-volume 170 within each insert 160. As noted above, the inserts 160 are each open at the top and bottom ends so as to provide fluid communication between the internal sub-volumes 170 and the rest of the device 100.

[0108] The shape of each insert 160 and their arrangement within the device body 110 further defines a plurality of inter-insert sub-volumes 172 located between the inserts 160 and a plurality of external sub-volumes 175 further located between the inserts 160 and the sidewall 115 of the device body 110. These external volumes 175 and inter-insert sub-volumes 172 are delimited at each end by the top of the insert wall 165 at one end and the bottom of the insert wall 165 and the base 118 of the device, such that they extend in this device 100 from the base 118 of the device body 110 to the top of the inserts 160. Specifically, the shape of each insert 160 causes the insert 160 to be spaced apart from at least one of the other inserts 160 and, further, from the vial sidewall 115. The inter-insert sub-volumes 172 and external subvolumes 175 are each in fluid communication with the rest of interior chamber 120 and internal sub-volumes 170 through the upper portion of the device body 110 and through movement of the inserts 160.

[0109] Accordingly, there are three main types of sub-volume: internal sub-volumes 170, interinsert sub-volumes 172 and external sub-volumes 175. Those between the external surfaces 166 of the insert walls 165 of the inserts 160 within the interior chamber 120 are inter-insert sub-volumes 172 and those between the insert walls 165 of the inserts 160 and the sidewall 115 of the device body 110 are external sub-volumes 175. The inter-insert sub-volumes 172 defined between the external surfaces 166 of the insert walls 165, have a maximum dimension across the width (i.e. as measured along the axis parallel to that defined by the insert wall 165 and the cylindrical shape, from the top-down view of the Fig. IB) equal to the maximum internal dimension of the internal sub-volume 170, but the shape formed by virtue of the convex shape of the outer surfaces of the insert wall 165 means that a significant portion of these interinsert sub-volumes 172 has a cross-sectional dimension significantly lower than maximum. As can be seen from Fig. IB, the cross-sectional shape is that of a three- or four-pointed star, with regions tapering to a point. In these regions, the dimensions are significantly smaller creating narrow regions in which a significant portion of emitted particles will be deposited outside of the solution 105, such as in the insert walls 165, the sidewall 115 of the device body 110 or outside of the device 100, thereby significantly reducing radiolysis. Further, despite at leastsome these inter-insert sub-volumes 172 having a smaller total volume than the internal subvolumes 170, the presence of these inter-insert sub-volumes 172 across the device 100 overall provides a significant increase in the total volume of solution 105 within regions where the distance of any particular emitted particle to a wall, such as an insert wall 165 or sidewall 115, is reduced as compared to just utilising the internal sub-volumes 170. This significantly increases the utility and usability of the devices 100.

[0110] The external sub-volumes 175 are located between the insert walls 165 of the inserts 160 and the sidewall 115 of the device body 110. In this device 100, by virtue of convex shape of the inserts 160, these have similar narrow regions between the inserts 160 to the inter-insert sub-volumes 172, where the radiolysis rate will be very low, in addition to the central regions where the volume is high. Further, by virtue of the curvature of the sidewall 115 of the device body 110, the maximum dimension across the width of these external sub-volumes 175 is less than the dimension in the same plane for the internal sub-volumes 170 creating smaller subvolumes.

[0111] Compared to use of the device 100 alone for storage of solutions comprising radioisotopes, the provision of the internal sub-volumes 170, inter-insert sub-volumes 172 and external sub-volumes 175 provides the advantages discussed above. The configuration of the insert array 150 within the interior chamber 120 allows for the distribution of the solution 105 across multiple smaller volumes, improving the stability of radioisotope solutions stored or processed in the device 100. The fluid communication between the internal sub-volumes 170, inter-insert sub-volumes 172 and the external sub-volumes 175 allows for the distribution of the solution 105 across multiple small volumes without significantly impeding handling or requiring specialist equipment to use the device 100. The solution 105 can flow into the internal sub-volumes 170 within the inserts 160 and the inter-insert sub-volumes 172 and external sub-volumes between the inserts 160 and between the inserts 160 and the sidewall 115 of the device body 110.

[0112] In use, solution 105 can be provided to the interior chamber 120 via the opening 161. The fluid communication between the various parts within the interior chamber 120 means that no specialist equipment is required to provide fluid to the internal sub-volumes 170, inter-insert sub-volumes 172 and external sub-volumes 175 and, instead, this can simply be achieved by filling the interior chamber 120 to the desired height. Further, as the inserts 160 are moveable relative to the device body 110 and one another, if manipulation is required to fill a particular region, this can be done either through individual movement of inserts 160 or through inverting of the device 100 when closed, for example - i.e. in a straightforward manner. Removal of the solution 105 is similarly straightforward, and the structure permits removal using, for example,a syringe with a needle inserted into just one of the sub-volumes 170, 175 or a part of the interior chamber 120 and reliance on the fluid communication to allow for removal of the solution 105.

[0113] The device 100 of Figs. 1A and IB is provided as an example of an implementation of the devices disclosed herein. It will be appreciated that modifications can be made, in addition to those discussed in detail above. For example, with respect to the inserts 160, these could have numerous sizes and shapes. Further, not all inserts 160 within the device need to be identical and the device 100 may comprise inserts 160 of different sizes and / or shapes. To increase fluid handling useability, the inserts 160 may be raised from the base 118 so as to permit fluid flow through the bottom opening of the inserts 160 and / or there may be additional openings through the hollow cylindrical insert wall 165 to permit further fluid communication between the internal sub-volumes 170, inter-insert sub-volumes 172 and the external subvolumes 175.

[0114] The dimensions of the device body 110 and the inserts 160 can be selected for the particular solutions and radioisotopes that they are to be used for, including the diameter of the inserts 160 (e.g. as measured across the circular cross-section shown in Fig. IB) and the wall thicknesses of the insert wall 165, the sidewall 115 and the base 118. In some cases, the insert array 150 may be designed such that at least some of the internal sub-volumes 170, inter-insert sub-volumes 172 and the external sub-volumes 175 are of similar size (maximum dimension and / or volume). This can help to ensure a uniform distribution of the solution 105 within the device 100. In other cases, these may be different sizes, for example, the insert array 150 may be designed such that the internal sub-volumes 170 are larger than the inter-insert sub-volumes 172 and external sub-volumes 175, or such that the external sub-volumes 175 are larger than the internal sub-volumes 170 and inter-insert sub-volumes 172.

[0115] Figs. 2A and 2B schematically depict a further device 200 according to the disclosure. The device 200 is for receiving a solution 105 comprising a radioisotope and has a similar structure to the device 100 of Figs. 1A and IB, in that it comprises a cylindrical device body 210, an insert array 250 provided in the device body 210 and a solution 105 provided in the device body 210. In a similar manner to device 100, the device body 210 comprises a base 218 and a sidewall 215 extending from the base 218. The sidewall 215 and base 218 define an interior chamber 220 for receiving the solution 105.

[0116] The device 200 also comprises an insert array 250 provided within the interior chamber 220. In this device 200, the insert array 250 is a single unitary body comprising multiple insert walls 265. In this insert array 250, however, the insert walls 256 are connected (e.g. bonded or fused) along their length to the adjacent insert walls 265 so as to form a single, unitary insertarray 250. In this way, this particular insert array 250 can be thought of a plurality of inserts fused together. Each insert wall 265 has an internal surface 266 which delimits a first type of internal sub-volume 270 (the hollow void defined by each cylindrical insert wall 265 provides an enclosed internal sub-volume 270); a further type of internal sub-volume 270’ provided between the convex surfaces of the insert wall 265 between the insert walls (similar to the interinsert sub-volumes 172 of Fig. IB) and an external surface 267 which in part delimits an external sub-volume 275. The insert walls 265 in this insert array 250 effectively define hollow cylinders in a manner similar to the insert array 150 of device 100 with an opening 261 at the top end and an opening at the bottom end (not depicted) for fluid communication between the internal sub-volumes 270, 270’ define and the remainder of the interior chamber.

[0117] The shape of the external surface 267 of the insert walls 265 and the arrangement within the insert array 250 also further defines the plurality of external sub-volumes 275. For example, between the external surface 267 of adjacent the insert walls 265 around the outside of the insert array 250 and the sidewall 215 of the device body 210. These external sub-volumes 275 are delimited at each end by the length of the insert array 250, such that they extend in device 200 from the base 218 to the top of the insert array 250. The insert array 250 in this device 200 is sized and arranged with cylindrical insert walls 265 so that there are plural external subvolumes 275 around the circumference of the device body 210, delimited by the outermost part of each of the insert walls 265 contacting the inner surface of the sidewall 215. It will be appreciated that smaller diameters of insert array 250 may create a single external sub-volume 275 or a combination of smaller and larger external sub-volumes 275.

[0118] The external sub-volumes 275 are in fluid communication with the rest of interior chamber 220 and internal sub-volumes 270, 270’ through the upper portion of the device body 210. Although not depicted, the insert array 250 can be spaced apart from base 218 to provide further fluid communication via the openings 261 to each of the internal sub-volumes 270, via openings at the bottom of the insert array 250 to second type of internal sub-volumes 270’ and external sub-volumes 275 adjacent the base 218 of the device body 210.

[0119] In use, solution 105 can be provided to the interior chamber 220 via the opening 116 so that solution 105 can enter the internal sub-volumes 270, 270’ and external sub-volumes 275. Alternatively, the insert array 250 can be inserted after the solution 105 has been added. The unitary nature of insert array 250 is advantageous because it can make insertion and removal of the insert array 250 straightforward. For example, it can be inserted after solution 105 has been added without requiring significant handling. Similarly, it can be removed prior to removal of solution 105 from the device body 210 so as to simplify the removal of solution 105. The second type of internal sub-volume 270’ and the external sub-volumes 275 may bemore precisely defined within the unitary structure. The unitary nature of the insert array 250 may also provide improved structural integrity and stability within the device. Additionally, the interconnected design of a unitary insert array 250 may enhance fluid distribution and communication between sub-volumes.

[0120] Although the device 200 of Fig. 2A has been depicted in the upright orientation, it will be appreciated that this device 200 could represent a device operated in a horizontal orientation, such as a separation device (e.g. a column) or a part of a reactor, such as portion of a fluid conduit within a reactor. In such a configuration, base 218 would not be present (i.e. there would be an open end) or base 218 would have an opening therein to permit fluid flow therethrough, such that solution 105 can pass from one end of the device 200 to the other with the internal sub-volumes 270, 270’ and external sub-volumes 275 acting as channels for the solution 105. In this way, the shape and configuration of the internal sub-volumes 270, 270’ and external sub-volumes 275 is such that these separate the flow into several sub-channels defined by the open ended internal sub-volumes 270, 270’ and external sub-volumes 275 so as to reduce radiolysis, but which otherwise have a minimal impact on the flow rate which can be provided through the device 200. The same is also true for the device 100 of Figs. 1 A and IB.

[0121] Figs. 3A, 3B and 4 provide schematic depictions of alternative devices 300, 400 according to the disclosure, which differ in the type of insert array 350, 450.

[0122] Fig. 3A provides a schematic view of a device 300 for receiving a solution 105 comprising a radioisotope stood on its end and Fig. 3B provides a front end view of the device 300. The device 300 comprises a device body 310 having an overall cylindrical shape. The device body 310 comprising a base 318 on which the device body 310 is resting in Fig. 3 and sidewalls 315 which form the remainder of the cylindrical shape extending out from the base 318 and arcing around a central axis extending in a plane perpendicular to that of the view of Fig. 3 to form an enclosed interior chamber 320 with a circular cross-section. This device 300 takes the form of a channel, having openings at either end of the cylindrical device body 310.

[0123] The device 300 further comprises an insert array 350 provided within the interior chamber 320. The insert array 350 is formed of multiple (four), discrete inserts 360, each insert 260 having an insert wall 365. The inserts 360 in this device 300 are each an elongate member or plate forming the insert wall 365 and having a length equal to that of the device body 310 and having a curved profile across the width of the elongate member such that, from the end view of Fig. 3B and any cross-section along the length of the elongate member, each has a substantially C-shaped cross-section. As arranged in Figs. 3 A and 3B, the concave surface of each insert 260 forms the external surface 366 and the convex surface forms the internal surface 367. The inserts 360 forming the insert array 350 are arranged within the interior chamber 320that the concave surfaces of the C-shape cross-section of each insert 360 faces outwardly towards the sidewall 315 of the device body 310 with the internal surfaces 367 of the insert walls 365 facing internally towards and in contact with one another. The opposing longitudinal edges of the external surface 367 of the insert walls 365 contact the sidewall 315. Accordingly, the insert walls 265 are sized and arranged so that each insert 360 occupies approximately a quarter of the circumference of the sidewall 315. The concave external surfaces 366 of the inserts 360 form enclosed external sub-volumes 375 together with the sidewall 315 delimited around the circumference by the contact between the insert walls 365 and the sidewall 315. Similarly, the arrangement of the inserts 360 as the insert array 350 also forms an internal subvolume 370 delimited by the convex internal surfaces 367 of the individual insert walls 365, which are in contact with the insert walls 365 of the neighbouring inserts 360. This creates an internal sub-volume 370 within the insert array 350 and external sub-volumes 375 between the inserts 360 and the sidewall 315 of the device body 310.

[0124] The device 300 can accordingly be used as a conduit for a solution 105, for example as part of a reactor or separation device (e.g. a column), with the solution 105 entering one end of the device 300 and moving through the device 300 to the other. Alternatively, this could be used to store solution 105, for example, if closed at both ends. As a further modification, this could be used in a vertical orientation, with a base provided at one end of the interior chamber 320, for example.

[0125] Fig. 4 depicts a further device 400, which device 400 has a similar structure to the device 300 of Figs. 3A and 3B, with the exception being that the insert array 450 of the device 400 of Fig. 4 is provided as a single unitary body rather than being formed of individual inserts 360.

[0126] In particular, the device 400 comprises a device body 410 having a cylindrical shape and comprises a base on which the device body 410 is resting in the front end view of Fig. 4 and sidewalls 415 which extend from the base 418 and curve around to form the cylindrical shape and thereby enclosed interior chamber 420 around a central axis extending in a plane perpendicular to that of the view of Fig. 4. The device 400 takes the form of a channel, having openings at either end.

[0127] The device 400 further comprises an insert array 450 provided within the interior chamber 420. The overall shape of the insert array 450 and internal and external sub-volumes 470, 475 formed by the insert array 450 is similar to that of Figs. 3A and 3B. Specifically, the insert array 450 comprises four insert walls 465, each having an elongate form and a length equal to that of the device body 410, with a curved profile across the width of each insert wall 465 such that, from the end view of Fig. 4 and any cross-section along the length of the insert array 450, these insert walls 465 each have a substantially C-shaped cross-section. Theconcave surface of each insert wall 465 forms the external surface 466 and the convex surface of each insert wall 465 forms an internal surface 467. The insert array 450 is structured so that the concave surfaces of the C-shape cross-section of each insert wall 465 faces outwardly towards the sidewall 415 of the device body 410, with each of the four insert walls 465 of this particular example sized and arranged so that occupies approximately a quarter of the circumference of the sidewall 415. The concave external surfaces 466 of the insert walls 465 thus form enclosed external sub-volumes 475 together with the sidewall 415, with the insert walls 465 each contacting the sidewall 415 to delimit the external sub-volumes 475. The insert array 450 is also structured so that the convex part of the insert walls 465 form an internal subvolume 470 delimited by the convex internal surfaces 467 of the individual insert walls 465. This creates an internal sub-volume 470 within the insert array 460 and a series of external subvolumes 475 between the inserts and the sidewall 415 of the device body 410.

[0128] As with the device 300 of Figs. 3A and 3B, the device 400 can accordingly be used as a conduit for a solution 105, for example as part of a reactor or separation device (e.g. a column), with the solution 105 entering one end of the device and moving through the device to the other. Alternatively, this could be used to store solution 105, for example, if closed at both ends. As a further modification, this could be used in a vertical orientation, with a base provided at one end of the interior chamber 420, for example.

[0129] Although the devices 100, 200, 300, 400 of Figs. 1A to 4 have been depicted with the respective internal sub-volumes 170, 270, 370, 470 in fluid communication with one another and the remainder of volumes within the device, it will be appreciated that these could be fluidly isolated instead. For example, the inserts 160 of the device 100 of Figs. 1A and IB could be closed at either end (with at least one being removable to allow filling).

[0130] FIG. 5 depicts a device 500 in the form of a vial for receiving a solution 105 comprising a radioisotope. The device 500 includes a device body 510 having a cylindrical shape with a base 518 and a cylindrical sidewall 515 extending upwards from the base 518. The sidewall 515 and base 518 enclose an interior chamber 520 for receiving the solution 105. An opening 516 is provided at the top of the device 500 through which the solution 105 can be provided to and removed from the interior chamber 520 of the device 500. A cap (not shown) can be used to close the opening 516 and thereby seal the interior chamber 520 of the device 500.

[0131] The device 500 also comprises a plurality of beads 582, each bead 582 having a substantially spherical shape. The beads 582 are arranged as a stack 580 provided on the base 518, with the beads 582 stacked on top of each and moveable relative to one another and relative to the device body 510 so that they can move within the interior chamber 520, as required.

[0132] The geometric (size and shape) of the beads 582 means that as they stack, the beads 582 define multiple fluidly connected sub-volumes 570, 575 within the interior chamber 520. The solution 105 containing the radioisotope is provided in these fluidly connected sub-volumes 570, 575. Specifically, the shape of each bead 582 causes the bead 582 to be spaced apart from the adjacent beads 582 in the stack and, further, from the device sidewall 515, creating regions or sub-volumes 570 between the beads 582 in the stack 680 (which can be referred to as “interparticle” sub-volumes 570). As will be appreciated, this creates a series of fluid pathways formed by interconnected sub-volumes 570 through stack 680 running between the beads 582. As solution 105 is added to the device body 510, it will flow down through the pathways and fill the internal sub-volumes 570.

[0133] In addition, the spacing of the beads 582 away from the internal surface of the sidewall 515 of the device body 510, creates further sub-volumes 575, which can be referred to as “external” sub-volumes 575. These external sub-volumes 575 are in fluid communication with the rest of interior chamber 520 and sub-volumes 570 between beads 582.

[0134] Each bead 582 has a maximum dimension of from 20 pm to 8 mm. In the particular depicted example, the beads 582 each have the same maximum dimension. By virtue of the shape (substantially spherical) of the beads 582 and the regular stacking within stack 680, this creates internal sub-volumes 570 having a maximum dimension equal to that of the beads 582. However, it will of course be appreciated that beads 582 could have different sizes and shapes in other embodiments.

[0135] The beads 582 in the stack 680 are movable relative to one another. This allows for flexibility in the arrangement of the beads 582 and the resulting sub-volumes 570 and external sub-volumes 575, but also improved handling. In use, solution 105 can be provided to the interior chamber 520 via the opening. The fluid communication between the various subvolumes within the interior chamber 520 means that no specialist equipment is required to provide the solution 105. Filling can simply be achieved by pouring solution into the interior chamber 520 to the desired height. Further, as the beads 582 are moveable relative to the device body 510 and one another, if manipulation is required to fill a particular region, this can be done either through individual movement of beads 582 directly or through tipping (e.g. inverting) of the device 500. Removal of the solution 105 is similarly straightforward, and the structure permits removal using, for example, using a syringe with a needle inserted into stack of beads 582 - reliance on the fluid communication will cause fluid to be drawn out from all of the internal sub-volumes 570 and external sub-volumes 575.

[0136] Figs. 6A, 6B and 7 depict devices 600, 700 in the form of vials for receiving a solution 105 comprising a radioisotope. The devices 600, 700 each include a device body 610, 710having a cylindrical shape with a base 618, 718 and a cylindrical sidewall 715, 815 extending upwards from the respective base 618, 718. The sidewall 615, 715 and base 618, 718 of each encloses an interior chamber 620, 720 for receiving the solution 105. An opening 616616, 616616 is provided at the top of each device 600, 700 through which the solution 105 can be provided to and removed from the respective interior chamber 620620, 720.

[0137] Each device 600, 700 further comprises an insert array 650, 750 provided within the respective interior chamber 620620, 720.

[0138] The insert array 650 of the device 600 of Figs. 6A and 6B is a monolithic structure formed from silicone or another polymer. The insert array 650 comprises a plurality of discrete cells, such as discrete interconnected open cells, each cell defined by an insert wall 665 and forming an internal surface, thereby delimiting a plurality of internal sub -volumes 670 within the interior chamber. The undulating shape of the external surface of the insert array 650 facing the sidewall 615 of the device body 610 provides the external surface of the insert walls 665 and further defines a plurality of external sub-volumes 675.

[0139] The insert array 750 of the device 700 of Fig. 7 is also a monolithic structure formed from silicone or another polymer. The insert array 750 comprises a plurality of interconnected open cells each defined by an insert wall 765 and forming an internal surface, thereby delimiting a plurality of internal sub-volumes 770 within the interior chamber. There is also a second type of internal sub-volume 770’ in this insert array 750, in the form of a cutout which extends through the insert array 750 from top to the bottom of the insert array 750. In the depicted example, this is a cylindrical hollow extending along the length of the insert array 750. Thus, the internal surface of the insert wall 765 defining the cylindrical hollow define the second type of the internal sub-volume 770’ and the external surface defines the external subvolumes 775. Specifically, the undulating shape of the external surface of the insert array 750 facing the sidewall 715 of the device body 710 provides the external surface of the insert walls 765 and further defines a plurality of external sub-volumes 775.

[0140] Insert arrays 650, 750 of the types depicted in Figs. 6A, 6B and 7 advantageously can be produced using manufacturing techniques such as 3D printing.

[0141] Although the devices of Figs. 1 to 7 have been discussed with respect to solutions, it will be appreciated that the devices disclosed above may be used with other types of compositions, such as powders.

[0142] Although the devices of Figs. 5 to 7 have been depicted in the upright orientation, it will be appreciated that these devices could represent a device operated in a horizontal orientation, such as a separation device (e.g. a column) or a part of a reactor, such as portion of a fluid conduit within a reactor. In this arrangement, the part labelled as base may be an open end orhave an opening therein to permit fluid flow therethrough, such that solution can pass from one end of the device to the other.Examples

[0143] Various examples are provided below to demonstrate how the insert arrays and particles disclosed herein have been tested for improvements in reducing radiolysis.Example 1

[0144] 10 mL and 5mL glass vials (HPLC vials) were used in this example to determine reduction of radiolysis using insert arrays. Three of the lOmL vials were filled with insert arrays comprised of separate inserts as set out in Table 2, below. Vials 1 and 5 are comparative and do not contain any insert arrays (i.e. they are empty). Vials 2 to 4 contain insert arrays and are according to the disclosure. Specifically, each of vials 2 to 4 were filled with discrete cylindrical tubes of different sizes, as set out in Table 2. The cylindrical tubes are each of constant diameter and are open at both ends, in a similar manner to that of the insert array 150 of Fig. 1. Schematic drawings of the vials 2 to 4 are provided in Figs. 8A to 8C, respectively. As can be seen in Figs. 8A to 8C, each of vials 2 to 4 contained a different number of tubes and different sizes (see also Table 2, below). Further, although the tubes are of the same size within each vial, it will be appreciated that the shape need not be identical (and indeed, in other examples, different sizes and shapes within the same device could be used). The vials were each filled with a solution comprising 200 pL of Img / mL N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[l,5-a]pyrimidine-3-acetamide (“DPA714”) (DPA714 Reference, 200328-03, DPA-714, 1 mg, Pharmasynth) together with 95-97 mCi / mL of [18F]F-. Where the vials contained insert arrays (i.e. Vials 2 to 4), the vials were filled with the inserts in situ. The same volume of solution was provided to each vial. It is known that emitted particles from [18F]F- causes DPA714 to degrade and, therefore, radiolysis can be tracked by tracking the degradation of DPA714 in solution. This is reported as “percentage degradation (%)” in Table 2, below, and depicted in the graph of Fig. 9 (referred to as %radiolysis).

[0145] The vials were left overnight (23 hours after time of mixing [18F]F- with DP A714). The contents of each vial was analyzed by reverse phase HPLC using a LunaCl 8(2) HPLC column 5 pm, 4.6 mm x 250 mm with an isocratic mobile phase (50% MeCN in aqueous 100 mM ammonium formate, pH 4.5). The HPLC column was heated to 30°C. Injection volume was 10 pL and UV detection was performed using a PDA detector. 254 nm was used for quantification of intact DPA714. The calculation of %degradation was made by dividing the area under the peak with the area under the peak for a reference sample comprising DPA714 only, below.Table 2: Vials of Example 1* NMR tubes 3mm OD, borosilicate glass, via Sigma Aldrich (WIMWG3000750-50EA), #WG-3000-7-50A, Lot 3110, Wilmad NMR tubes 3mm diam, Type 1 Class A, high throughput ** NMR tubes 5mm OD, borosilicate glass, via Sigma Aldrich, Z271987-1PAK Lot# 3110, Wilmad NMR tubes 5mm diam., precision, frequency 100 MHz, L 7 in. Pcode 1003143122

[0146] It can be seen that the empty vials Vial 1 and Vial 5 have the greatest percentage (%) rate of degradation of DPA714 and, hence, the highest levels of radiolysis. Each of Vials 2 to 4, which contain the inserts, decreases radiolysis significantly. Compared to Vial 1, Vials 2 and 3 decreased radiolysis by over 60% (Vial 2 a 63% reduction and Vial 3 a 65% reductioncompared to Vial 1). The larger diameter insert array of Vial 4 was still effective, decreasing radiolysis compared to Vial 1 by around 45%. It will be appreciated that, despite the larger diameter of the internal sub-volumes in Vial 4, the presence of these and the presence of the internal sub-volumes and, further, the formation of the external sub-volumes still reduced radiolysis through the mechanisms discussed herein. Despite the presence of the insert arrays, the solution was readily introduced and removed from Vials 2 to 4 and no reduction in volume of solution was necessary.Example 2

[0147] 10 mL glass vials (HPLC vials) were used in this example to determine reduction of radiolysis using beads. The radiochemical stability of a 85 mCi / mL solution of [18F]-radiolabeled phenoxyanilide ([18F]FEPPA) was monitored over time, with a measurement at 5 hours after the solution was provided to each vial. A first 10 mL glass vial was used as a comparative example (herein “Vial 7”) and did not comprise any inserts or beads. A second 10 mL glass vial was filled with glass beads (Sigma Aldrich, Solid Glass Beads, Z273627- 1EA, diameter 2 mm, borosilicate glass) (herein “Vial 8”). The same volume of the [18F]FEPPA was added to each and the stability monitored and reported as a percentage of radiochemical purity. This was determined by reverse phase HPLC with an in-line UV and gamma detector. LunaC18(2) HPLC column 5pm, 4.6 mm x 250 mm using isocratic mobile phase conditions 45% 100 mM aqueous ammonium formate in 55% acetonitrile, 1 ml / min, column at ambient temperature. 1.3 pL injection volumes at approximately 5 hours after the solution was provided to each vial. The radiochemical purity was measured by integrating the signals from the gamma detector and compared to the purity at the start.

[0148] Fig. 10 depicts a graph showing the results of Example 2. At time 0, both of the solutions in Vials 7 and 8 had a radiochemical purity of 99.65%. After 5 hours, the radiochemical purity of the solution in Vial 7 was reduced to 83.81%, whereas the radiochemical purity of the solution in Vial 8 with the beads, after 5 hours, remained at 98.61%. Accordingly, the presence of the beads in Vial 8 significantly reduced the degradation of the compounds therein and vastly improved the radiochemical purity of the solution compared to the use of a vial alone.Example 3

[0149] Example 3 further explored reduction of radiolysis. 10 mL glass vials (HPLC vials) were used in this example to determine reduction of radiolysis using beads. A first 10 mL glass vial was used as a comparative example (herein “Vial 9”) and was empty (i.e. did not comprise an insert array or beads). A second 10 mL glass vial according to the disclosure (herein “Vial10”) was filled with glass beads having a diameter of 2 mm and a substantially spherical shape. A third 10 mL glass vial according to the disclosure (herein “Vial 11”) was filled with glass beads having a diameter of 4 mm and a substantially spherical shape.

[0150] Vials 9 to 11 were each filled with a solution comprising a N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[l,5-a]pyrimidine-3-acetamide (“DPA714”) together with varying concentrations of [ 18F]F-, as set out in Table 3, below. Where the vials contained beads (i.e. Vials 10 and 11), the vials were filled with the beads in situ. The same volume of solution was provided to each vial. The amount of radiolysis which had occurred in each of the vials was determined using HPLC (as set out for Example 1, above) after approximately 24 hours, for each solution concentration.Table 3: Vials of Example 3

[0151] As can be seen from Table 3 and Fig. 11, radiolysis was significantly reduced in the vials comprising beads (i.e. Vials 10 and 11), even though these beads have diameters which are significantly above the average path length for positrons emitted during 18F decay. It can also be seen that the 2 mm beads of Vial 10 provided this to a greater extent than the 4 mm beads of Vial 11. Moreover, it is also apparent that the use of beads allows for the use ofsolutions with higher radioactivity concentrations before the inflection point at which radiolysis significantly increased occurs. In other words, whereas for the solution, the inflection point of radioactivity concentration beyond which radiolysis significantly increases with increased radioactivity concentration was reduced. Vials 10 and 11 accordingly enabled much more concentrated solutions to be stable compared to Vial 9 without beads. It can also be seen that the 2 mm beads of Vial 10 provided this to a greater extent than the 4 mm beads of Vial 11.Further examples

[0152] Clause 1. A device for receiving a composition comprising a radioisotope, the device comprising:a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; andan insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls,wherein the one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber; andwherein at least one external sub-volume is formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the device sidewalls; andwherein the device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes.

[0153] Clause 2. The device of clause 1, wherein the device comprises a plurality of insert walls and a plurality of internal sub-volumes, wherein each of the plurality of internal sub-volumes is defined by a corresponding one of the plurality of insert walls.

[0154] Clause 3. The device of clause 2, wherein the insert array comprises a plurality of discrete inserts, each insert comprising at least one of the plurality of insert walls, optionally wherein at least one inter-insert sub-volume is defined between the insert wall of at least two inserts.

[0155] Clause 4. The device of clause 3, wherein each insert comprises an insert body comprising one of the plurality of insert walls, each insert wall defining a tubular structure enclosing an internal sub-volume; and wherein the plurality of inserts are arranged within theinterior chamber of the device in contact with an adjacent insert of the plurality of inserts, with the tubular structure of each insert body causing the respective insert to be spaced apart from at least one of the other inserts of the plurality of inserts so as to provide a further internal sub volume therebetween.

[0156] Clause 5. The device of clause 2, wherein the insert array is a unitary assembly comprising the plurality of insert walls.

[0157] Clause 6. The device of any preceding clause, wherein each insert wall of the one or more insert walls comprises a plurality of internal surfaces, each of the plurality of internal surfaces enclosing a corresponding internal sub-volume.

[0158] Clause 7. The device of any of clauses 1 to 6, wherein each insert wall delimits an insert chamber, the insert chamber defining the internal sub-volume; and wherein each insert chamber comprises a maximum dimension of from 20 pm to 8 mm, optionally from 100 pm to 8 mm.

[0159] Clause 8. The device of any of clauses 1 to 7, wherein the device comprises a plurality of external sub-volumes formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the device sidewalls.

[0160] Clause 9. The device of any preceding clause, wherein a cross-section dimension of the internal sub-volume is below at least one of (i) the beta(+) or beta(-) range of the radioisotope or (ii) the alpha range of the radioisotope.

[0161] Clause 10. The device of any preceding clause, wherein the at least one internal subvolume is in fluid communication with the at least one external sub-volume.

[0162] Clause 11. The device of any preceding clause, wherein the at least one external subvolume has a maximum dimension of less than or equal to the diameter of the interior chamber of at least one of the respective inserts.

[0163] Clause 12. The device of any preceding clause, wherein the insert array comprises a plurality of insert walls and together the plurality of inserts enclose an internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber.

[0164] Clause 13. The device of any preceding clause, wherein the device is a vial for holding a solution comprising a radioisotope.

[0165] Clause 14. Use of a device to receive a composition comprising a radioisotope, the device comprising:a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; andan insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls,wherein the one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber; andwherein at least one external sub-volume is formed within the interior chamber between the one or more insert walls and the at least one of the internal surface of the device sidewalls; andwherein the device comprises a plurality of the internal sub -volumes and / or a plurality of the external sub-volumes.

[0166] Clause 15. Use according to clause 14, wherein the device is according to any of clauses 1 to 13.

[0167] Clause 16. A device for receiving a composition comprising a radioisotope, the device comprising:a device body comprising one or more device walls and an interior chamber delimited at least in part by an interior surface defined by the one or more device walls, wherein the interior chamber is for receiving a composition comprising a radioisotope;a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected subvolumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 pm to 8 mm; anda composition comprising a radioisotope, wherein the composition is provided in the fluidly connected sub-volumes.

[0168] Clause 17. The device of clause 16, wherein each particle has a maximum dimension of from 100 pm to 8 mm, optionally from 500 pm to 8mm.

[0169] Clause 18. The device of clause 16 or clause 17, wherein at least one of the plurality of particles is movable relative to another of the plurality of particles.

[0170] Clause 19. The device of any of clauses 16 to 18, wherein each particle has a shape selected from substantially spherical, substantially spheroidal, substantially ellipsoidal, substantially ovoidal, substantially toroidal, or substantially cylindrical.

[0171] Clause 20. The device of any of clauses 16 to 19, wherein each of the plurality of particles comprises or consists of a glass, a glass-ceramic, a ceramic or a polymer, optionally wherein the each of the plurality of particles comprises a core comprising or consists of a glass, a glass-ceramic, a ceramic or a polymer and a coating surrounding the core.

[0172] Clause 21. The device of clause 20, wherein each particle of the plurality of particles comprises an outer surface in contact with the composition, and wherein the outer surfaces of the particles have a combined surface concentration of SiOH and SiO- moieties of less than 4 nm-2.

[0173] Clause 22. The device of clause 21, wherein each particle of the plurality of particles a polymer, the polymer defining the outer surface of each particle.

[0174] Clause 23. The device of any of clauses 16 to 22, wherein the device is a vial for holding a solution comprising a radioisotope.

[0175] Clause 24. Use of a device to receive a solution comprising a radioisotope, the device comprising: a device body comprising one or more device walls and an interior chamber delimited at least in part by an interior surface defined by the one or more device walls, wherein the interior chamber is for receiving a composition comprising a radioisotope;a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected subvolumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 pm to 8 mm; and a composition comprising a radioisotope, wherein the composition is provided in the fluidly connected sub-volumes.

[0176] Clause 25. Use according to clause 24, wherein the device is according to any of clauses 16 to 23.

Claims

CLAIMS1. A device for receiving a composition comprising a radioisotope, the device comprising:a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by the one or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; andan insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls,wherein the one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber;wherein at least one external sub-volume is formed within the interior chamber between the one or more insert walls and the internal surface of the one or more device sidewalls; andwherein the device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes; andwherein the device further comprises a composition comprising a radioisotope provided to each internal sub-volume and external sub-volume.

2. The device of claim 1, wherein the insert array comprises a plurality of insert walls and the device comprises a plurality of internal sub-volumes, wherein each of the plurality of internal sub-volumes is defined by a corresponding one of the plurality of insert walls.

3. The device of claim 2, wherein the insert array comprises a plurality of discrete inserts, each insert comprising at least one of the plurality of insert walls.

4. The device of claim 3, wherein each insert comprises an insert body comprising one of the plurality of insert walls, each insert wall defining a tubular structure enclosing an internal subvolume; andwherein the plurality of inserts are arranged within the interior chamber of the device in contact with an adjacent insert of the plurality of inserts, with the tubular structure of each insert body causing the respective insert to be spaced apart from at least one of the other inserts of the plurality of inserts so as to provide a further internal sub-volume therebetween.

5. The device of claim 2, wherein the insert array is a unitary assembly comprising the plurality of insert walls.

6. The device of any preceding claim, wherein each insert wall of the one or more insert walls comprises a plurality of internal surfaces, each of the plurality of internal surfaces enclosing a corresponding internal sub-volume.

7. The device of any preceding claim, wherein each insert wall delimits an insert chamber, the insert chamber defining the internal sub-volume; and wherein each insert chamber comprises a maximum dimension of from 20 pm to 8 mm, optionally from 100 pm to 8 mm.

8. The device of any preceding claim, wherein the device comprises a plurality of external subvolumes formed within the interior chamber between the one or more insert walls and the internal surface of the device sidewalls.

9. The device of any preceding claim, wherein a cross-section dimension of the internal subvolume is below at least one of (i) the beta(+) or beta(-) range of the radioisotope or (ii) the alpha range of the radioisotope.

10. The device of any preceding claim, wherein the at least one internal sub-volume is in fluid communication with the at least one external sub-volume.

11. The device of any preceding claim, wherein the at least one external sub-volume has a maximum dimension of less than or equal to the diameter of the interior chamber of at least one of the respective inserts.

12. The device of any preceding claim, wherein the insert array comprises a plurality of insert walls and together the plurality of inserts enclose an internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber.

13. Use of a device to receive a composition comprising a radioisotope, the device comprising:a device body comprising one or more device sidewalls defining an internal surface and an interior chamber delimited at least in part by the internal surface defined by theone or more device sidewalls, wherein the interior chamber is for receiving a composition comprising a radioisotope; andan insert array provided within the interior chamber of the device body, the insert array comprising one or more insert walls,wherein the one or more insert walls enclose at least one internal sub-volume so as to at least in part separate the internal sub-volume from the remainder of the interior chamber; andwherein at least one external sub-volume is formed within the interior chamber between the one or more insert walls and the internal surface of the one or more device sidewalls; andwherein the device comprises a plurality of the internal sub-volumes and / or a plurality of the external sub-volumes.

14. A device for receiving a composition comprising a radioisotope, the device comprising:a device body comprising one or more device walls and an interior chamber delimited at least in part by an interior surface defined by the one or more device walls, wherein the interior chamber is for receiving a composition comprising a radioisotope;a plurality of particles provided within the interior chamber, wherein the particles are arranged as a stack and defining a plurality of fluidly connected sub -volumes between the plurality of particles within the interior chamber and wherein each particle has a maximum dimension of from 20 pm to 8 mm; anda composition comprising a radioisotope, wherein the composition is provided in the fluidly connected sub-volumes.

15. The device of claim 14, wherein each particle has a maximum dimension of from 100 pm to 8 mm, optionally from 500 pm to 8mm.

16. The device of claim 14 or claim 15, wherein at least one of the plurality of particles is movable relative to another of the plurality of particles.

17. The device of any one of claims 14 to 16, wherein each particle has a shape selected from substantially spherical, substantially spheroidal, substantially ellipsoidal, substantially ovoidal, substantially toroidal, or substantially cylindrical.

18. The device of any one of claims 14 to 17, wherein each of the plurality of particles comprises or consists of a glass, a glass-ceramic, a ceramic or a polymer, optionally wherein the each of the plurality of particles comprises a core comprising or consists of a glass, a glassceramic, a ceramic or a polymer and a coating surrounding the core.

19. The device of claim 18, wherein each particle of the plurality of particles comprises an outer surface in contact with the composition, and wherein the outer surfaces of the particles have a combined surface concentration of SiOH and SiO" moi eties of less than 4 nm'2.

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