Patent Application
20230317308
The field of the disclosure relates generally to production of radionuclides and, more particularly, to a container closure for use in systems and methods for preparing radionuclide solutions.
Radiopharmaceuticals, drugs that incorporate a radioactive element (i.e., a radionuclide), are used in nuclear medicine for diagnostic and/or therapeutic purposes. Radionuclides typically used in nuclear medicine include technetium-99m (Tc-99m), indium-111 (In-111), thallium-201 (TI-201), fluorine-18 (F-18), and copper-64 (“Cu-64”), among others. Radionuclides may be produced naturally, or via decay of a long-lived parent (i.e., a radionuclide generator), or by direct production (e.g., proton- or neutron-induced reaction). In the production of at least some radionuclides and radiopharmaceuticals, it is desirable to concentrate a radionuclide precursor solution to dryness or near-dryness. In production methods where a radionuclide precursor is isolated in a strong acid or organic solvent, solvent evaporation is often used as the penultimate step before final reconstitution of the precursor in a biocompatible solvent, either for direct injection or incorporation into a biomolecule (e.g., monoclonal antibody). In the case of radiopharmaceutical production, purification of a radiopharmaceutical agent using a reversed-phase C18 column may require subsequent removal of a bioincompatible organic solvent (e.g., acetonitrile). Accordingly, a need exists for processes and apparatuses that facilitate concentrating liquid radionuclide precursor solutions to dryness or near-dryness.
This Background section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.
In one aspect, a closure includes a body extending longitudinally along a central longitudinal axis from a first, upper surface to a second, lower surface. The body defines a cavity extending into the body from the lower surface to a third, interior surface. The cavity is sized and shaped to receive a portion of a container therein. The body includes a shroud extending from the interior surface to the lower surface, and a container insert depending from the interior surface and positioned within the cavity. The container insert is sized and shaped to fit within an opening of the container. The body further includes an outlet flow path in fluid communication with the cavity, and at least one inlet flow path in fluid communication with the cavity. The at least one inlet flow path is positioned and oriented to generate a vortex gas flow within the container when connected thereto.
In another aspect, a system includes a radiation containment chamber, a remote manipulator connected to the radiation containment chamber, a container positioned within an interior of the radiation containment chamber, a closure connected to the container and including a body including an outlet flow path and at least one inlet flow path, an evaporation station positioned within the interior of the radiation containment chamber and including at least one heating element for applying heat to the container, and a gas handling system including a suction line connected to an outlet of the outlet flow path. The at least one inlet flow path of the closure generates a vortex gas flow within the container when suction is applied to the container by the suction line.
In yet another aspect, providing, within a radiation containment chamber, a container having a radioactive liquid disposed therein, and connecting, using a remote manipulator, a closure to the container such that the closure seals against the container. The closure includes at least one inlet flow path and an outlet flow path. The method further includes directing a flow of gas through the at least one inlet flow path of the closure to generate a vortex gas flow within the container.
Various refinements exist of the features noted in relation to the above-mentioned aspects. Further features may also be incorporated in the above-mentioned aspects as well. These refinements and additional features may exist individually or in any combination. For instance, various features discussed below in relation to any of the illustrated embodiments may be incorporated into any of the above-described aspects, alone or in any combination.
Corresponding reference characters indicate corresponding parts throughout the several views of the drawings.
The evaporation station 104 and container assembly 110 are enclosed within the containment chamber 102 to shield operators from nuclear radiation emitted by radioactive materials within the containment chamber 102 (e.g., radioactive liquid 112). The containment chamber 102 generally includes an enclosure 114 constructed of nuclear radiation shielding material designed to shield the surrounding environment from nuclear radiation. The enclosure 114 defines an interior 116 in which the evaporation station 104 is positioned. Suitable shielding materials from which the containment chamber 102 may be constructed include, for example and without limitation, lead, depleted uranium, and tungsten. In some embodiments, the containment chamber 102 is constructed of steel-clad lead walls forming a cuboid or rectangular prism. Further, in some embodiments, the containment chamber 102 may include a viewing window constructed of a transparent shielding material. Suitable materials from which viewing windows may be constructed include, for example and without limitation, lead glass.
The evaporation station 104 includes one or more devices to evaporate the radioactive liquid 112. Suitable devices for use in the evaporation station 104 include, for example and without limitation, heating elements, such as hot plates, resistive heaters, fluid-based heaters or heat exchanges, and gas-fired heaters. In the illustrated embodiment, the evaporation station 104 includes a hot plate 118 having a selectively-adjustable temperature that allows an operator to set a desired temperature to which the container assembly 110 and radioactive liquid 112 are heated during an evaporation process.
The gas handling system 106 is operable to supply and remove gas from the containment chamber 102, such as from within the evaporation station 104. In some embodiments, the gas handling system 106 is configured to remove gases and volatile compounds generated during an evaporation process at the evaporation station 104. The gas handling system 106 can include any suitable components that enables the gas handling system 106 to function as described herein, including, for example and without limitation, fluid conduits, pumps, pressurized-gas supplies, filters, traps, and combinations thereof.
In the illustrated embodiment, the gas handling system 106 includes a pump 120, a suction line 122 connected to an inlet 124 of the pump 120, and one or more gas supply lines 126. The pump 120 and associated electronics and controls are positioned outside of the radiation containment chamber 102 to shield the components from radiation. The pump 120 can generally include any suitable pump that enables the gas handling system 106 to function as described herein, including, for example and without limitation, a reciprocating pump, a rotary pump, a centrifugal pump, a positive displacement pump, and combinations thereof. The suction line 122 is connected to the inlet 124 of the pump 120, and includes an inlet end 128 that connects to the container assembly 110 to provide suction thereto. Each gas supply line 126 is connected to a pressurized gas source 130 (e.g., compressor, pressurized inert gas supply tanks, etc.), and includes an outlet end 132 that connects to the container assembly 110 to provide a flow of gas thereto. The suction line 122 and gas supply lines 126 can generally include any suitable fluid conduit that enables the gas handling the system 100 to function as described herein, including, for example and without limitation, tubes, hoses, pipes, and combinations thereof. Additionally, the suction line 122 and gas supply lines 126 can include rigid conduits, flexible conduits, and combinations thereof. The inlet end 128 of the suction line 122 and the outlet end 132 of each of the gas supply lines 126 can include suitable fluid couplers and/or adapters to facilitate connection to the container assembly 110. Suitable fluid couplers and adapters include, for example and without limitation, Luer fittings, threaded couplers, compression fittings, and combinations thereof.
The illustrated gas handling system 106 also includes a trap 134 connected to the suction line 122 upstream of the pump inlet 124. The trap 134 collects volatile species (e.g., HCI gas) and/or water vapor (e.g., using a desiccant) evaporated from the radioactive liquid 112 during the evaporation process, as well as small particulates entrained in the gas flow through the suction line 122.
The remote manipulator 108 is connected to the radiation containment chamber 102, and allows manipulation of objects (e.g., the container assembly 110) within the containment chamber 102 from a remote location, such as outside the containment chamber 102. Examples of remote manipulators suitable for use with the system 100 include telemanipulators, autonomous or semi-autonomous systems (e.g., robotic arms), and manual instruments that extend an operator’s reach (e.g., long forceps). In the example embodiment, the remote manipulator 108 is illustrated in the form of a telemanipulator that allows an operator outside of the containment chamber 102 to manipulate objects (e.g., the container assembly 110) within the containment chamber 102. The telemanipulator can have any suitable telemanipulator configuration that enables the system 100 to function as described herein. In the illustrated embodiment the telemanipulator includes an operator handle or controller 136 positioned outside of the radiation containment chamber 102, an articulated arm 138 connected to the controller 136 and positioned within the containment chamber 102, and an end effector 140 positioned at a distal end of the articulated arm 138. The operator controller 136 can be used, for example, to control a position, orientation, and/or state (e.g., opened or closed) of the end effector 140. In some embodiments, the end effector 140 includes mechanical fingers or clamps that allow an operator to grip or clamp objects (e.g., the container assembly 110) within the radiation containment chamber 102. Although only one telemanipulator is shown in
The container assembly 110 includes a container 142 and a cap or closure 144 connected to the container 142. The container 142 is generally configured to hold a volume of liquid therein. The container 142 may be sized to hold any suitable volume of the radioactive liquid 112 therein. In some embodiments, the container 142 is sized to hold a relatively small volume of the radioactive liquid 112 therein, such as less than 100 mL, less than 80 mL, less than 60 mL, less than 40 mL, less than 30 mL, less than 20 mL, or even less than 10 mL. In other embodiments, the container 142 may be sized to hold a volume of the radioactive liquid 112 greater than 100 mL. The container 142 is constructed of a chemically inert material, including, for example and without limitation, glass (borosilicate glass, Pyrex®), quartz, polyoxymethylene (e.g., Delrin®), polycarbonate, polytetrafluoroethylene (e.g., Teflon™), polypropylene, and other plastics compatible with the solvent being evaporated.
The closure 144 is configured to seal against a portion of the container 142 when connected thereto to control the flow of gas within the container 142 during an evaporation process. In the example embodiment, the closure 144 is connected directly to the container 142. In other embodiments, the closure 144 can be connected to or otherwise include an adapter or peripheral component to facilitate connection to containers of varying shapes and sizes (e.g., containers with different sized and/or shaped openings). In some embodiments, for example, the closure 144 is connectable to a plurality of different adapters, each sized and shaped to fit a different container such that the closure 144 is connectable to and usable with a plurality of different containers (e.g., vials, centrifuge tubes, round bottom flasks, etc.). The closure 144 of the illustrated embodiment is designed to facilitate evaporation of the radioactive liquid 112 within the container 142. For example, as described further herein, the closure 144 includes at least one vortex-generating feature that generates a vortex and associated centrifugal forces within the container 142 during the evaporation process, increasing the surface area of the liquid 112 and thereby accelerating the evaporation process.
During an evaporation process, the container 202 having a volume of the radioactive liquid 112 (shown in broken lines in
The closure 204 seals against a portion of the container (e.g., the sidewall 208 and/or the neck 210), thereby providing a closed system to inhibit or prevent the introduction of environmental contaminants (e.g., trace metallic contaminants) into the container 202. Additionally, the closure 204 provides a dedicated path for collection of gases and other volatile species evaporated during the evaporation processes via the gas handling system 106. Compounds evaporated from the radioactive liquid 112 can be highly corrosive (e.g., HCI gas and water) and cause corrosion of components within the containment chamber 102, and/can accumulate and be released in unwanted areas if not properly collected and disposed of. As described in greater detail herein, the closure 204 also facilitates the evaporation process by increasing the rate of evaporation. In particular, embodiments of the closures described herein are configured to introduce gas flow into the container 202 in such a way that the liquid 112 is stirred in a vortex motion, thereby increasing the surface area of the liquid 112 and accelerating the evaporation rate.
The closure 204 may have any suitable construction that enables the system 100 and container assembly 200 to function as described herein. With additional reference to
In the illustrated embodiment, the body 302 extends longitudinally along a central longitudinal axis 318 from a first, upper surface 320 to a second, lower surface 322. The body 302 includes four side surfaces 324 extending from the upper surface 320 to the lower surface 322. Each of the side surfaces 324 has a rectangular shape and is generally flat or planar. The upper surface 320, lower surface 322, and four side surfaces 324 define the body exterior surface 304.
The body 302 defines a cavity 326 that extends into the body 302 from the lower surface 322 to a third, interior surface 328. The cavity 326 is sized and shaped to receive a portion of the container 202 therein, such as the neck 210, shoulder portion 214, and/or sidewall 208. In the illustrated embodiment, the cavity 326 is shaped cylindrically, although in other embodiments the cavity 326 may be shaped differently, such as square, rectangular, polygonal, ellipsoidal, or any other shape that enables the closure 204 to function as described herein.
The body 302 includes a shroud 330 that extends from the interior surface 328 to the lower surface 322. The shroud 330 includes a radial inner surface 332 that at least partially defines the cavity 326. The body 302 also includes a container insert 334 that depends from the interior surface 328 and is positioned within the cavity 326. The container insert 334 is sized and shaped to fit within the container opening 212 when the closure 204 is connected to the container 202. As shown in
In the illustrated embodiment, the container insert 334 includes an outlet extension 336 depending from a lower surface 338 of the container insert 334. The outlet extension 336 defines the outlet flow path inlet 316. Additionally, the inlet flow path outlets 312 are defined adjacent the lower surface 338 of the container insert 334. The outlet flow path inlet 316 is axially offset from each of the inlet flow path outlets 312 to reduce or minimize interference between incoming gas flow and exiting gas flow. In the illustrated embodiment, the outlet flow path inlet 316 is positioned lower than (i.e., closer to the second, lower surface 322 of the body 302) than the inlet flow path outlets 312. In other embodiments, the inlet flow path outlets 312 may be positioned lower than (i.e., closer to the second, lower surface 322) than the outlet flow path inlet 316. In the illustrated embodiment, the container insert 334 and outlet extension 336 are shaped cylindrically, where the outlet extension 336 has a smaller diameter than the remainder of the container insert 334. In other embodiments, the container insert 334 may be shaped other than cylindrical.
The example closure 204 includes two inlet flow paths 306, and a single outlet flow path 308. In other embodiments, the closure 204 may have fewer than two inlet flow paths 306 (e.g., one inlet flow path), or greater than two inlet flow paths 306 (e.g., three inlet flow paths, four inlet flow paths, etc.). Additionally, the closure 204 may have more than one outlet flow path 308 in other embodiments.
As shown in
As noted above, the inlet flow paths 306 are configured as vortex generating features to facilitate evaporation of a liquid within the container 202. More specifically, the inlet flow paths 306 are oriented at suitable angles and positioned at suitable locations on the closure 204 such that gas flow directed through the inlet flow paths 306 creates a vortex air or gas flow within the container 202. In the illustrated embodiment, each inlet flow path 306 is oriented at an oblique angle 340 (
The outlet flow path 308 is parallel to and coaxial with the central longitudinal axis 318 in the example embodiment. In other embodiments, the outlet flow path 308 may be other than parallel to and/or coaxial with the central longitudinal axis 318.
When the closure 204 is connected to a container, such as the container 202, and gas is directed through the inlet flow paths 306 and the outlet flow path 308, a vortex is generated within the container 202, as illustrated by arrows 216 in
Gas flow may be directed through the inlet flow paths 306 and outlet flow path 308 using the gas handling system 106 (shown in
The closure 204 seals against a portion the container 202 such that gas flow into and out of the container is permitted only through the inlet flow paths 306 and the outlet flow path 308. The closure 204 may include one or more seals or sealing materials to facilitate forming a seal against the container 202. In some embodiments, for example, the closure 204 may include one or more elastomeric seals (e.g., O-rings) that engage a portion of the container 202 to form a seal therewith when the closure 204 is inserted over the top of the container 202. The elastomeric seals may be positioned and held in place within grooves defined in the closure body 302. In some embodiments, for example, the body 302 has a groove defined along the radial inner surface 332 of the shroud 330, and an elastomeric seal is positioned within the groove such that the seal engages the shoulder portion 214 and/or sidewall 208 of the container 202 to form a seal against the container 202. Additionally or alternatively, the interior surface 328 and/or a radial outer surface of the container insert 334 may include a groove and an elastomeric seal positioned therein to facilitate forming a seal between the closure 204 and the container 202.
The closure 204 of the illustrated embodiment is particularly suited for use in a radioactive environment (e.g., in the production of radionuclides and radionuclide precursors). For example, the closure 204 is constructed of materials resistant to both radiation degradation and corrosive gases evaporated during an evaporation process (e.g., HCI gas and water). Suitable materials include, for example and without limitation, polytetrafluoroethylene (e.g., Teflon™), perfluoroalkoxy alkanes, fluorinated polymers, polycarbonate, polylactic acid, polyether ether ketone (PEEK), polyoxymethylene (e.g., Delrin®), glass, metal alloys (e.g., stainless steel), plated or coated alloys (e.g., stainless steel coated with ethylene chlorotrifluoroethylene (e.g., Halar®)), and combinations thereof. The closure 204 may also be free of metals that might otherwise corrode in the presence of gases evaporated during an evaporation process. The closure 204 can be constructed using various methods, including, for example and without limitation, machining, casting, molding, additive manufacturing (e.g., 3D printing), and combinations thereof. Additionally, the closure 204 is designed to facilitate movement by a remote manipulator, such as the telemanipulators, which are used in high radiation environments (e.g., radiation containment chamber 102) to limit an operator’s exposure to nuclear radiation (e.g., gamma radiation). More specifically, the closure 204 includes at least one pair of opposing flats 342 (
In use, the closure 204 is connected to the container 202 during an evaporation process to facilitate evaporation of a liquid (e.g., radioactive liquid 112, shown in
Gas is then directed through the container 202 using, for example, the gas handling system 106. In particular, gas flows into the container 202 through the inlet flow paths 306, and out of the container 202 through the outlet flow path 308. Gas flow is directed through the inlet flow paths 306 such that a vortex fluid flow is generated within the container 202. As noted above, for example, the inlet flow paths 306 in the illustrated embodiment are configured as vortex-generating features such that the inlet flow paths 306 generate a vortex air flow (illustrated by arrows 216 in
The suction line 122 and/or gas supply lines 126 of the gas handling system 106 may be connected to the closure 204 prior to the closure 204 being connected to the container 202. For example, the gas supply lines 126 and/or suction line 122 may be connected to the closure 204 manually by a human operator, prior to the closure 204 being introduced into the radiation containment chamber 102, and/or prior to the radiation containment chamber 102 being exposed to radioactive material. Alternatively, the suction line 122 and/or gas supply lines 126 may be connected to the closure 204 while the closure 204 is within the radiation containment chamber 102 (e.g., using the remote manipulator 108).
The liquid within the container 202 is heated (e.g., using the hot plate 118) while gas flows through the container 202. The vortex air flow generated by the closure 204 within the container 202 facilitates evaporation of the liquid by increasing the surface area of the liquid during the evaporation process. Once a desired amount of liquid has evaporated from the container 202, the closure 204 may be removed from the container 202 (e.g., using the remote manipulator 108) and the container 202 may be moved to another area of the radiation containment chamber 102 or a separate radiation containment chamber for further processing.
When introducing elements of the present invention or the embodiment(s) thereof, the articles “a”, “an”, “the” and “said” are intended to mean that there are one or more of the elements. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.
As various changes could be made in the above constructions and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
This application claims priority to U.S. Provisional Pat. Application Serial No. 63/072,641, filed Aug. 31, 2020, the disclosure of which is hereby incorporated by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2021/047564 | 8/25/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63072641 | Aug 2020 | US |
