The field of the disclosure relates generally to formulating radioactive materials and, more particularly, to systems and methods for formulating radioactive liquids using disposable containers.
Radioactive material is used in nuclear medicine for diagnostic and therapeutic purposes by injecting a patient with a small dose of the radioactive material, which concentrates in certain organs or regions of the patient. Radioactive materials typically used for nuclear medicine include Germanium-68 (“Ge-68”), Strontium-87m, Technetium-99m (“Tc-99m”), Indium-111m (“In-111”), Iodine-131 (“I-131”) and Thallium-201. Sometimes, the radioactive materials are generated from another radioactive material, such as Molybdenum-99 (Mo-99).
Prior to use, the radioactive materials may be formulated from a raw, concentrated form into a form having a desired concentration. For example, radioactive liquids may be homogeneously mixed, pH-adjusted, sampled, diluted, and dispensed. Sometimes, the radioactive liquids are contained within a reusable glass vessel during formulation. After formulation, the vessels are washed to remove radioactive residue and then placed in long-term radiologically shielded storage. After the vessels have been stored for a time sufficient to allow any radioactive material to decay, the vessels may be cleaned, sterilized, and reused. Accordingly, these vessels can be expensive to produce and use. As a result, the cost to formulate radioactive materials is increased. Also, processing the vessels for reuse generates radioactive waste, such as rinse fluids used to remove radioactive materials from the vessels. In addition, personnel may be exposed to radiation when handling the vessels during and after formulation.
Accordingly, a need exists for an inexpensive formulation container that does not require long-term radiologically-shielded storage, and reduces operator exposure to radiation.
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 disposable container for use in formulating a radioactive liquid includes a flexible sidewall defining an interior space for containing the radioactive liquid during formulation. The flexible sidewall is constructed of sterile, pyrogen-free material to prevent contamination of the radioactive liquid. The flexible sidewall includes a first portion and a second portion. The disposable container also includes an access port and a dispense port. The access port is defined by the first portion of the flexible sidewall to provide access to the interior space. The dispense port is defined by the second portion of the flexible sidewall for the radioactive liquid within the interior space to be dispensed through.
In another aspect, a system for formulating a radioactive liquid includes a nuclear radiation containment chamber including an enclosure constructed of a nuclear radiation shielding material. The system also includes a disposable container and a positioning device positioned within the interior of the enclosure. The disposable container includes a flexible sidewall defining an interior space for containing the radioactive liquid during formulation. The positioning device includes a support configured to support the disposable container on the positioning device and an actuator operatively connected to the support and configured to rotate the support. A dispense pump is connected to the disposable container in fluid communication with the interior space to dispense the radioactive liquid from the interior space.
In yet another aspect, a method of formulating radioactive liquid contained within a disposable container includes connecting the disposable container to a positioning device and rotating an actuator of the positioning device to position the disposable container in a first position. The method also includes formulating the radioactive liquid within the interior space while the disposable container is in the first position. The method further includes rotating the actuator of the positioning device to position the disposable container in a second position and dispensing the liquid from the disposable container using a dispense pump. The radioactive liquid is directed towards a dispense port of the disposable container when the disposable container is in the second position.
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.
Example systems and methods of the present disclosure provide disposable containers for use in formulating radioactive liquids. Accordingly, embodiments reduce exposure of personnel to radiation and reduce the resources required to formulate radioactive liquids. In particular, embodiments eliminate the requirement to clean and store reusable vessels that may be contaminated with radioactive materials. In addition, some embodiments provide a positioning device that positions the disposable containers during formulation of the radioactive liquids within the disposable container.
As used herein, the terms “formulate”, “formulation”, and “formulating” refer to combining materials to form a material having a desired concentration and pH.
The formulation apparatus 102 is enclosed within the containment chamber 104 to shield operators and radiation-sensitive electronics of the controller 106 from nuclear radiation emitted by radioactive materials within the containment chamber 104. The containment chamber 104 generally includes an enclosure 108 constructed of nuclear radiation shielding material designed to shield the surrounding environment from nuclear radiation. The enclosure defines an interior in which the formulation apparatus 102 is positioned. Suitable shielding materials from which the containment chamber 104 may be constructed include, for example and without limitation, lead, depleted uranium, and tungsten. In some embodiments, the containment chamber 104 is constructed of steel-clad lead walls forming a cuboid or rectangular prism. Further, in some embodiments, the containment chamber 104 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.
During formulation, raw material may undergo a series of operations or processes before the material reaches a target state. For example, in some embodiments, raw radioactive material (e.g., Mo-99) is quality control tested, chemically treated if necessary, and pH adjusted prior to diluting the raw radioactive material to a desired final target concentration. The raw radioactive material may be diluted to the final target concentration by combining the raw radioactive material with another liquid, such as water for injection (WFI). After the raw radioactive material has been diluted, the formulated liquid may be dispensed to a suitable containment vessel for storage. In some embodiments, all formulation tasks may be performed at a single station, i.e., a formulation station. In further embodiments, at least one of the described tasks may be performed at a separate station.
The positioning device 110 is configured to support the disposable container 108 during formulation of radioactive liquids within the disposable container 108. The positioning device 110 includes a table, broadly a support, 114 and an actuator 116 operatively connected to the table 114 for positioning the table 114. As will be described in more detail below, the actuator 116 is configured to rotate the table 114 about a rotation axis 118 to position the disposable container 108 during formulation.
In this embodiment, the table 114 includes a plate 120 and a sidewall 122 extending from and partially circumscribing the plate 120. The plate 120 and the sidewall 122 define a cavity 124 configured to receive the disposable container 108. A plurality of connectors 126 are positioned within the cavity 124 to secure the disposable container 108 to the table 114. The connectors 126 include at least one hook and an engagement member. In other embodiments, the disposable container 108 may be positioned on the table 114 and supported in any manner that enables the formulation apparatus 102 to operate as described. For example, in some embodiments, the plate 120 and the sidewall 122 are omitted and the disposable container 108 is secured to one or more arms. In other embodiments, the disposable container 108 is connected to the positioning device 110 using any suitable connector including, for example and without limitation, fasteners, straps, hooks, clamps, adhesives, and cords.
In the illustrated embodiment, the actuator 116 is operatively connected to the table 114 by a rotatable shaft 128. The table 114 has a first end 130 connected to the rotatable shaft 128 and a second end 132 positioned distal from the rotatable shaft 128. Accordingly, the table 114 pivots or rotates about the rotation axis 118 when the rotatable shaft 128 is rotated. In other embodiments, the table 114 may rotate about any axis. For example, in some embodiments, the rotatable shaft 128 is connected to the table 114 intermediate the first end 130 and the second end 132 and the table 114 rotates about an axis intermediate the first end 130 and the second end 132.
In reference to
In reference to
In the illustrated embodiment, the drive mechanism 139 suitably includes a miter gearbox that is operatively connected to the motor and the rotatable shaft to rotate the rotatable shaft 128 during operation of the motors 138. In other embodiments, the actuator 116 may include any drive mechanism that enables the positioning device 110 to operate as described.
In addition, the formulation apparatus 102 of this embodiment includes three pumps 112. Specifically, the formulation apparatus 102 includes a dispense pump 112, a circulation pump 112, and a redundant pump 112. As will be described in more detail below, the dispense pump 112 is configured to pump liquids out of the disposable container 108. The circulation pump 112 is configured to circulate liquids contained in the disposable container 108. The redundant pump 112 may be configured to perform the functions of the circulation pump 112 and the dispense pump 112. Accordingly, the redundant pump 112 may be put in service to reduce down time of the formulation apparatus 102 if one of pumps 112 is inoperable. In the illustrated embodiment, each of the pumps 112 is a peristaltic pump. In other embodiments, the formulation apparatus 102 may include any pump that enables the formulation apparatus 102 to operate as described.
Each of the pumps 112 is operatively connected to, or driven by, a motor 142 positioned beneath the clean work surface 140. The motors 142 are configured to drive the pumps 112 such that the pumps 112 direct liquid flow through tubing connected to the pumps 112. The motors 142 are suitably connected to the controller 106 (shown in
The formulation apparatus 102 is configured to prevent contamination of the radioactive liquid during formulation. For example, in the illustrated embodiment, the motors 138, 142 are positioned below a clean work surface 140 to inhibit contamination of the work area. In other embodiments, any component of the system 100 (shown in
In other embodiments, the disposable container may be constructed in other ways. For example, in an alternative embodiment, the disposable container may include one or more ports disposed in the seams of the bags, e.g., three ports welded into a bottom seam of the bag. In another embodiment, one or more tubes extends through the seam into the bag. In other embodiments, a port flange may be attached to a seam and have an oval shape. In still other embodiments, rather than separate components welded to the disposable container, the bottom seam includes tubing welded directly thereto, similar to an intravenous (IV) fluid bag. Generally, the ports may be formed in any manner that enables the disposable container to function as described.
The disposable container is suitably sterile, pyrogen free, and compatible with radioactive materials, such as Molybdenum-99 (Mo-99), Germanium-68 (“Ge-68”), Strontium-87m, Technetium-99m (“Tc-99m”), Indium-111m (“In-111”), Iodine-131 (“I-131”) and Thallium-201. For example, the disposable container 108 may be made of materials including, without limitation, linear low-density polyethylene (LLDPE), ethylene vinyl acetate (EVA), polypropylene, nylon, polychlorotrifluoroethene (PCTFE), and fluorinated ethylene propylene (FEP). In other embodiments, the disposable container 108 may be made of other materials in any suitable manner.
The disposable container 108 may be disposed of after use because the disposable container 108 is inexpensive to replace. Accordingly, cleaning and/or long term shielded storage of the disposable container 108 may not be necessary. In addition, the disposable container 108 does not require cleaning validation which is required for reusable pharmaceutical vessels. As a result, the time and resources required to handle the disposable container 108 may be reduced. In addition, radioactive waste, such as rinse liquids, may be reduced. Also, the disposable container 108 is not prone to shattering, which may occur with other vessels such as glass vessels.
In reference to
The disposable container 108 includes a first portion 148, a second portion 152, and at least one opening or port. In the illustrated embodiment, the disposable container 108 includes an access port 154, a dispense port 156, and circulation ports 158. The access port 154 is positioned in the first portion 148. The dispense port 156 and the circulation ports 158 are positioned in the second portion 152. In other embodiments, the disposable container 108 may include any port or opening that enables the disposable container 108 to function as described.
The disposable container 108 is sized to hold a predetermined volume within interior space 146. In some embodiments, the disposable container 108 has a volume of approximately 50 liters. The volume of the disposable container 108 may be limited by seams, ports, and other features of the disposable container 108. In this embodiment, the disposable container 108 may contain between about 0.5 liters and about 25 liters of the radioactive liquid. In other embodiments, the disposable container 108 may have any volume that enables the disposable container 108 to function as described.
In reference to
In the illustrated embodiment, the access port 154 is substantially centered relative to the width 174 of the disposable container 108. The access port 154 is positioned a longitudinal distance 175 from the lateral edge 186 of the first portion 148. In some embodiments, the longitudinal distance 175 may be in a range of about 1 inch to about 10 inches. In the illustrated embodiment, the longitudinal distance 175 is about 5.5 inches.
The access port may be selectively closed by a removable cap 160 to prevent liquid entering and exiting the interior space 146. The cap 160 removably connects to a collar 155 of the access port 154. In the illustrated embodiment, the collar 155 includes threads that engage threads of the cap 160 to enable the cap 160 to be screwed into the collar 155. In addition, the collar 155 is configured to engage one of the connectors 126 of the positioning device 110 (shown in
In reference to
The dispense port 156 may be used to discharge liquid from the interior space 146. For example, the liquid may be discharged through dispense tubes 162 connected to the dispense port 156. At least one of the pumps 112 is configured to regulate flow of the liquid through the dispense tubes 162. In other embodiments, liquid may be dispensed from the dispense port 156 in any manner that enables the formulation apparatus 102 (shown in
A clamp 164 may be connected to the dispense tubes 162 adjacent the dispense port 156 to restrict flow through the dispense tubes 162. Accordingly, the clamp 164 prevents liquids from being trapped in the dispense tubes 162 when liquid is not being directed through the dispense tubes 162 by the pumps 112. In some embodiments, the clamp 164 may be manipulated by an operator from the exterior of the radiation containment chamber 104 using devices such as telemanipulators.
Each circulation port 158 is circular and has a circulation port ID 179. The circulation port ID is suitably in a range of about 0.25 inches to about 0.5 inches, and in this embodiment, the circulation port ID is about 0.375 inches. In other embodiments, the disposable container 108 may include any dispense port 156 that enables the disposable container 108 to function as described.
The circulation ports 158 may be used to circulate or mix liquid within the interior space 146. For example, the liquid may be circulated through circulation tubes 166 connected to the circulation ports 158. In particular, the circulation tubes 166 may extend from a first circulation port 158 to a second circulation port 158. At least one of the pumps 112 (shown in
In this embodiment, the dispense tubes 162 and the circulation tubes 166 are constructed of plastic materials, such as polyurethane, polyethylene, polypropylene, polycarbonate, and silicone. Accordingly, the tubes 162, 166 are able to withstand the radioactive environment. In addition, the tubes 162, 166 are compatible with radioactive liquids within the disposable container 108. Also, the tubes 162, 166 are gamma sterilized and pyrogen-free, and prevent contamination of the radioactive liquids. In other embodiments, the formulation apparatus 102 may include any tube that enables the formulation apparatus 102 to operate as described.
In reference to
In this embodiment, the dispense port 156 is positioned to enable substantially all of the liquid within the interior space 146 to be withdrawn through the dispense port 156. In particular, the dispense port 156 is centered relative to a transverse direction of disposable container 108 such that the angled seams 168 direct liquid towards the dispense port 156. In addition, the dispense port 156 is spaced a longitudinal distance 170 from the lateral edge 186 of the disposable container 108. In suitable embodiments, the longitudinal distance 170 is in a range from about 0.5 inches to about 2 inches. In the illustrated embodiment, the longitudinal distance 170 is approximately 1.4 inches. In other embodiments, the dispense port 156 may be positioned anywhere in the disposable container 108 that enables the disposable container 108 to function as described.
The circulation ports 158 of this embodiment are spaced a longitudinal distance 163 from a lateral edge 186 of the disposable container 108 and a lateral distance 165 from a longitudinal edge 190 of the disposable container 108. The longitudinal distance 163 is suitably in a range of about 0.5 inches to about 12.0 inches. In further embodiments, the lateral distance 165 is in a range of about 1.0 inches to about 20 inches. In the illustrated embodiment, the longitudinal distance 163 is about 3.4 inches and the lateral distance 165 is about 8.25 inches. In other embodiments, the circulation ports 158 may be positioned anywhere on the disposable container 108. In some embodiments, the circulation ports 158 may be omitted.
During operation, the positioning device 110 may move the disposable container 108 to facilitate accessing, dispensing, and/or treating the liquids within the disposable container 108. For example, the positioning device 110 may position the disposable container 108 such that the first portion 148 is positioned below the second portion 152. In particular, the first portion 148 may be positioned below the horizontal plane 136 (shown in
In another example, the disposable container 108 may be positioned such that the second portion 152 is positioned below the first portion 148. In particular, the second portion 152 may be positioned below the horizontal plane 136 and the first portion 148 may be positioned above the horizontal plane 136. Accordingly, liquid within the interior space 146 may be directed towards the circulation ports 158 and the dispense port 156. In the illustrated embodiment, the dispense port 156 is positioned adjacent the longitudinal edge 190 of the second portion 152 to facilitate substantially all the liquid within the interior space 146 being discharged through the dispense port 156.
In reference to
In reference
Also, in some embodiments, the formulation apparatus 102 may be used to dispense the radioactive liquid from the disposable container 108 after formulation. In particular, at least one of the pumps 112 may direct the liquid through the dispense tubes 162 until the desired amount of liquid has been dispensed. The disposable container 108 may be positioned any at any angle during the dispense operation. For example, the disposable container 108 may be positioned at an approximately 90° angle with the horizontal plane 136 such that liquid is directed towards the dispense port 156. The circulation tubes 166 may be raised to facilitate the liquid in the circulation tubes 166 flowing toward the dispense port 156 while the liquid is dispensed. Accordingly, substantially all liquid within the interior space 146 may be dispensed from the disposable container 108 in a relatively short time. For example, in some embodiments, a volume of about 500 milliliters of liquid can be drained from the disposable container 108 in approximately 45 seconds.
In reference to
In the illustrated embodiment, the eyelets 178 are spaced a longitudinal distance 184 from a lateral edge 186 of the disposable container 108 and a lateral distance 188 from a longitudinal edge 190 of the disposable container 108. In some embodiments, the longitudinal distance 184 is in a range of about 0.5 inches to about 5 inches. In further embodiments, the lateral distance 188 is in a range of about 0.5 inches to about 5 inches. In the illustrated embodiment, the longitudinal distance 184 is about 1.4 inches and the lateral distance 188 is about 1.4 inches. In other embodiments, the eyelets 178 may be positioned anywhere on the disposable container 108. In some embodiments, the eyelets 178 may be omitted.
Also, in the illustrated embodiment, each angled seam 180 extends a longitudinal distance 189 from the lateral edge 186 and a lateral distance 191 from the longitudinal edge 190. In some embodiments, the longitudinal distance 189 is in a range of about 1 inch to about 10 inches. In further embodiments, the lateral distance 191 is in a range of about 1 inch to about 10 inches. In the illustrated embodiment, the longitudinal distance 189 is about 5 inches and the lateral distance 191 is about 5 inches. In other embodiments, the disposable container 108 may include any seam that enables disposable container 108 to function as described.
In reference to
In reference to
The processor 915 may include one or more processing units (e.g., in a multi-core configuration). Further, the processor 915 may be implemented using one or more heterogeneous processor systems in which a main processor is present with secondary processors on a single chip. As another illustrative example, the processor 915 may be a symmetric multi-processor system containing multiple processors of the same type. Further, the processor 915 may be implemented using any suitable programmable circuit including one or more systems and microcontrollers, microprocessors, programmable logic controllers (PLCs), reduced instruction set circuits (RISC), application specific integrated circuits (ASIC), programmable logic circuits, field programmable gate arrays (FPGA), and any other circuit capable of executing the functions described herein. In this embodiment, the processor 915 controls operation of formulation apparatus 102 by outputting control signals to each of the positioning devices 110.
The memory device 910 is one or more devices that enable information such as executable instructions and/or other data to be stored and retrieved. The memory device 910 may include one or more computer readable media, such as, without limitation, dynamic random access memory (DRAM), static random access memory (SRAM), a solid state disk, and/or a hard disk. The memory device 910 may be configured to store, without limitation, application source code, application object code, source code portions of interest, object code portions of interest, configuration data, execution events and/or any other type of data.
In this embodiment, the controller 106 includes a presentation interface 920 that is connected to the processor 915. The presentation interface 920 presents information, such as application source code and/or execution events, to a user 925, such as a technician or operator. For example, the presentation interface 920 may include a display adapter (not shown) that may be coupled to a display device, such as a cathode ray tube (CRT), a liquid crystal display (LCD), an organic LED (OLED) display, and/or an “electronic ink” display. The presentation interface 920 may include one or more display devices. In this embodiment, the presentation interface 920 displays a graphical user interface for receiving information from the user 925, such as a target dispense or transfer volume.
The controller 106 also includes a user input interface 930 in this embodiment. The user input interface 930 is connected to the processor 915 and receives input from the user 925. The user input interface 930 may include, for example, a keyboard, a pointing device, a mouse, a stylus, a touch sensitive panel (e.g., a touch pad or a touch screen), a gyroscope, an accelerometer, a position detector, and/or an audio user input interface. A single component, such as a touch screen, may function as both a display device of the presentation interface 920 and the user input interface 930. In this embodiment, the user input interface 930 receives an input associated with a position of the disposable container 108 including, for example and without limitation, an angle measure.
In this embodiment, the controller 106 further includes a communication interface 935 connected to the processor 915. The communication interface 935 communicates with one or more remote devices, such as the formulation apparatus 102.
The controller 106 exchanges signals with the formulation apparatus 102 to control the formulation apparatus 102 during formulation of the radioactive liquid. In particular, the controller 106 may control the positioning device 110 to position the disposable container 108 at desired positions that facilitate at least one operation of the formulation apparatus 102. For example, the controller 106 may control the positioning device 110 such that the disposable container 108 is positioned to direct radioactive liquid towards the dispense port 156 (shown in
Embodiments of the systems and methods described provide several advantages over known systems. In particular, embodiments of the systems and methods provide a disposable container for use during formulation of radioactive liquids without need for cleaning validation or re-validation. For example, embodiments of the systems and methods described provide a disposable, shatter-proof, container including a flexible sidewall that is made of sterile, pyrogen-free materials and is compatible with radioactive materials. The disposable container provides several advantages over known containers, such as reusable vessels. For example, the disposable containers can be positioned in multiple positions during formulations. Also, the disposable containers can be disposed after use into solid waste without spilling liquid or contaminating hot cells. The containers do not require cleaning, validation, and/or storage in long-term radiation shielding storage, and typically have a 3 year shelf-life after gamma sterilization. The disposable containers provide increased visibility of contents of the disposable container because the disposable containers remain substantially transparent and do not darken in a single use, in contrast to materials such as glass which darken to near opaque translucence during use. In addition, the disposable containers prevent contamination because the disposable containers are almost fully sealed and inhibit most contamination from entering the container. Further, the disposable containers cannot shatter during use. In addition, the disposable containers do not contribute to personnel whole body or extremity exposure during processing or clean-up, and thus reduce operator exposure to radiation.
Embodiments of the formulation apparatus described provide positioning systems that accurately position the disposable container during formulation. The positioning system provides for precise positioning of the disposable container. For example, the positioning system positions the disposable container at an angle relative to a horizontal plane. In particular, an actuator of the positioning system is configured to rotate the disposable container through a broad range of angles. In addition, embodiments of the formulation apparatus described herein reduce contamination of the radioactive material during operation and reduce operator exposure to radiation. Further, the positioning system allows a disposable container to be lowered to remove pressure if the disposable container is punctured during use. In addition, the contents of the punctured disposable container may be pumped into another disposable container so that formulation activities can continue.
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.
Number | Name | Date | Kind |
---|---|---|---|
3576998 | Deutsch et al. | May 1971 | A |
3657541 | Deutsch et al. | Apr 1972 | A |
3857485 | Frank | Dec 1974 | A |
4282863 | Beigler et al. | Aug 1981 | A |
4472299 | Weisner et al. | Sep 1984 | A |
4783305 | Forrest | Nov 1988 | A |
5196001 | Kao | Mar 1993 | A |
6157036 | Whiting et al. | Dec 2000 | A |
20060048841 | Luehrsen et al. | Mar 2006 | A1 |
Number | Date | Country |
---|---|---|
0068605 | Jan 1983 | EP |
0118217 | Sep 1984 | EP |
1874671 | Jan 2008 | EP |
0033322 | Jun 2000 | WO |
2007114800 | Oct 2007 | WO |
Entry |
---|
International Search Report and Written Opinion of the International Searching Authority regarding PCT/US2016/069194 dated Nov. 10, 2017; pp. 1-17. |
Number | Date | Country | |
---|---|---|---|
20180158563 A1 | Jun 2018 | US |