WO2009029602A1

WO2009029602A1 - Valved radioisotope generator

Info

Publication number: WO2009029602A1
Application number: PCT/US2008/074271
Authority: WO
Inventors: Kevin Robert Martz
Original assignee: Mallinckrodt Inc.
Priority date: 2007-08-29
Filing date: 2008-08-26
Publication date: 2009-03-05

Abstract

One aspect of the invention relates to a radioisotope generator (10) having a fluid passage and a check valve (15) coupled with and in fluid communication with the fluid passage. Another aspect of the invention relates to a method of operation for a radioisotope generator in which an output of the radioisotope generator is automatically closed in response to a change in fluid pressure.

Description

VALVED RADIOISOTOPE GENERATOR

FIELD OF THE INVENTION

[0001] The invention relates generally to radioisotope generators capable of providing radioisotope solutions for use (e.g., alone or in combination with a tagging agent) in medical procedures.

BACKGROUND

[0002] This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present invention, 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 invention. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.

[0003] in the field of nuclear medicine, health-care professionais often diagnose and treat patients with radioactive materia!. Typically, the health-care professional injects a patient with a small dose of the radioactive material, which once in the patient's body, concentrates in certain organs or regions. Some radioactive materials naturally concentrate in a particular tissue: for example, iodine concentrates in the thyroid. Examples of radioactive material used for nuclear medicine include technetium-99m, indiunv113m, and strontium-87m. Frequently, the radioactive material is combined with a tagging or organ-seeking agent, which may assist in targeting/delivering the radioactive material to the desired organ or biologic region of the patient. A tagging agent may come in any appropriate form (e.g., a lyophiiized kit). These radioactive materials, alone or in combination with a tagging agent, are typically referred to as radiopharmaceuticals. At relatively low doses, a radiation imaging system (e.g., a gamma camera) may be used to image the organ or biological region that collects the radiopharmaceutical. Irregularities in the image often indicate a pathology, such as cancer. Higher doses of the radiopharmaceutical may treat pathologic tissue, such as cancer cells.

[0004] Many radiopharmaceuticals decay rapidly, so manufacturing and using them is a time-sensitive process. In some applications, shortly before use, the radiopharmaceutical is drawn from a radioisotope generator by eluting, or separating, the radiopharmaceutical from a more-stable radioactive material that decays into the desired radiopharmaceutical, e.g., molybdenum-99, as it decays, produces technetium-99m. During this process, the desired radioactive material is carried from the generator by a solvent, referred to as an eluant, and the radioisotope generator outputs a radioactive solution, referred to as an eluate, which is typically received in a vial connected to the output of the radioisotope generator.

[0005] The eluate, if not properly contained, can cause problems. When the elution ends, and the receiving vial is removed, the radioisotope generator could still carry eluate, which could leak from the output. If radioactive solution escapes from the radioisotope generator, it could be expensive to clean and inconvenience people who wish to avoid the spill, SUMMARY

[0006] Certain exemplary aspects of the invention are set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the invention might take and that these aspects are not intended to limit the scope of the invention. Indeed, the invention may encompass a variety of aspects that may not be set forth below.

[0007] One aspect of the invention relates to a radioisotope generator having a fluid passage (e.g., a conduit, channel, or volume through which fluid may flow), and a check valve (e.g., a one-way valve configured to obstruct the flow of a fluid when a pressure difference across the valve is below a threshold) in fluid communication (e.g., connected in a manner that allows fluid to flow there between) with the fluid passage. This check valve is configured to obstruct (e.g., seal) the fluid passage depending on a fluid pressure difference between an upstream side of the check valve and a downstream side of the check valve.

[0008] Another aspect of the invention relates to a method of operation for a radioisotope generator. In this method, an output of the radioisotope generator is automatically (e.g., at least partially without manual intervention) closed in response to a change in a fluid pressure. For instance, this change in the fluid pressure may refer to a decrease in a pressure difference across a check valve of the radioisotope generator below a threshold pressure of the check valve. An example of when this change in fluid pressure may take place may be when a radioisotope solution from the generator has at least partially filled a vial that is in fluid communication with the output of the radioisotope generator.

[0009] Various refinements exist of the features noted above in relation to the various aspects of the present invention. Further features may also be incorporated in these various aspects as well. These refinements and additional features may exist individually or in any combination. For instance, various features discussed below in relation to one or more of the illustrated embodiments may be incorporated into any of the above-described aspects of the present invention alone or in any combination. Again, the brief summary presented above is intended only to familiarize the reader with certain aspects and contexts of the present invention without limitation to the claimed subject matter.

BRIEF DESCRIPTION OF THE FIGURES

[0010] Various features, aspects, and advantages of the present invention will become better understood when the following detailed description is read with reference to the accompanying figures in which like characters represent like parts throughout the figures, wherein:

[0011] FIG. 1 is an elevation view of a radioisotope elution system;

[0012] FIG.2 is a cross-section of the radioisotope elution system of FIG. 1 ;

[0013] FIGS.3 and 4 are exploded views of the radioisotope elution system of FlG. 1 from different perspectives;

[0014] FIG. 5 is a top perspective view of the radioisotope elution system of FIG. 1 ;

[0015] FIG.6 is a cross-section of a generator;

[0016] FIG.7 is a perspective view of a valve; [0017] FIGS. 8-10 are orthogonal views of the valve of FIG.7;

[0018] FIGS. 11 and 12 are cross-sections of the valve of FIG.7 closed and open, respectively;

[0019] FIG. 13 is a flow chart of a fluid dispensing process;

[0020] FIG. 14 is a flow chart of a nuclear medicine process;

[0021] FiG. 15 is a diagram of a system for loading a syringe with a radioisotope; and

[0022] FIG. 16 is a diagram of a nuclear imaging system.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

[0023] One or more specific embodiments of the present invention wiil be described below. In an effort to provide a concise description of these embodiments, all features of an actual implementation may not be described in the specification. It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another. Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.

[0024] When introducing elements of various embodiments, the articles "a," "an," "the," "said," and the like mean that there are one or more of the elements. The terms "comprising," "including," "having," and the like are inclusive and mean that there may be additional elements other than the listed elements. Moreover, the use of "top," "bottom," "above," "below," and variations of these terms does not require any particular orientation of the components relative to some extrinsic reference (e.g., gravity). As used herein, the term "coupled" refers to the condition of being directly or indirectly connected or in contact. Additionally, the phrase "in fluid communication" indicates that fluid or fluid pressure may be transmitted from one object to another. As used herein, the word "exemplary" means "an example" and not necessarily preferred.

[0025] FIG. 1 shows an exemplary elution system 10, which includes an auxiliary shield 12 and a shielded elution assembly 14. The illustrated elution system 10 also has a valve 15, details of which are described below, that tends to mitigate some of the problems with conventional elution systems, As described below, in some embodiments, the valve 15 automatically closes an output of the elution system 10 in response to a drop in pressure across the output, as might occur after an evacuated vial is filled with eluate. Consequently, in some embodiments, the elution system 10 is believed to be iess likely to leak eluate after an elution. Examples of the valve 15 are described below after describing other components of the elution system 10. [0026] As mentioned, the illustrated elution system 10 has an auxiliary shield 12, which in this embodiment, includes a base 16, a lid 18, and a plurality of generally step-shaped, tiered modular rings 20 disposed one over the other between the base 16 and the lid 18 (see FlG. 2). Substantially all or part of the illustrated auxiliary shield 12 may be made of, or include, one or more radiation-shielding materials, such as lead, tungsten, depleted uranium, or tungsten-impregnated plastic. One or more of the components of the auxiliary shield 12 may be lined with, powder coated on, and/or embedded in other materials, such as a polymer. For instance, in some embodiments, at least a portion (e.g., a majority, or a substantial entirety) of the lid 18 of the assembly 12 may be over-molded with polycarbonate resin (or other polymer). Embedding or over-molding the shielding materials may enhance durability and/or facilitate formation of components with smaller dimensional tolerances than components made entirely out of shielding materials. Moreover, the modular aspect of the rings 20 may tend to enhance adjustment of the height of the auxiliary shield 12, and the step-shaped configuration may tend to contain some radiation that might otherwise escape through an interface between the rings 20. While FIGS. 1 and 2 depict one example of an auxiliary shield 12, it should be noted that, as with the other examples described herein, other types or configurations may be employed.

[0027] FIG.2 illustrates additional features of the elution system 10, including a radioisotope generator 22 (hereinafter, generator), an eluant source 24, and an eluate receptacle 26 disposed within the auxiliary shield 12. Herein, the term "eluant source" refers to a container (e.g., a vial or a conduit) that has or had an elution source fluid (e.g., oxidant-free, physiologic saline) disposed therein. In contrast, an "eluate receptacle" refers to a container for receiving eluate from a generator. As illustrated, the eluant source 24 is coupled to the generator 22 via one or more inlet needles 28 (e.g., a pair of hollow needles, one of which vents, and one of which is in direct fluid communication with a column (e.g., 308 of Fig. 6) of the generator 22), while the eluate receptacle 26 is coupled to the generator 22 via one or more outlet needles 30 (e.g., a single-hollow needle). When coupled to the generator 22, the eluant source 24 and eluate receptacle 26 may be said to be in fluid communication with the generator 22 (e.g., associated in a manner that enables fluid to flow from the eluant source 24 to eluate receptacle 26, through the generator 22). The eluate receptacle 26 is disposed inside an elution shield 32 of the shielded elution assembly 14. The elution shield 32 may exhibit any appropriate design, and may be made of lead, tungsten, tungsten impregnated plastic, another suitable radiation shielding material, or any combination thereof. [0028] Internally, the illustrated generator 22 includes an elution column 308 (Fig.6). This elution column includes a radioisotope and may exhibit any appropriate design/configuration. For instance, in some embodiments, the elution column 308 may be configured to allow separation of a daughter radioisotope from a patent radioisotope and output the desired radioisotope. Certain medically useful radioisotopes have relatively short half- iives (e.g., technetium-99 (99Tc) has a half-life of approximately 6 hours), To potentially expand the useful life of the generator 22, the elution column may include a more stable radioisotope that decays into the desired radioisotope (e.g., molybdenum-99 (99Mo) has a half-life of approximately 66 hours and decays into 99Tc). As the desired radioisotope is needed, it may be separated from the more stable radioisotope through an elution process, two examples of which are explained below. The generator 22 may include shielding configured to diminish radiation, and tubing to conduct fluids into and out of the elution column.

[0029] FIG.6 shows and example of the generator 22. In this embodiment, the generator 22 includes an outer container 302, shielding 304, an elution hood 306, and an elution column 308, which is disposed in the shielding 304. The illustrated outer container 302 may have a generally cylindrical shape, and the elution hood 306 may fit within, and align to, the outer container 302. In some embodiments, the elution hood 306, the outer container 302, and the shielding 304 may be made of, or include, a radiation-shielding material, such as one or more of those listed above. [0030] The shielding 304 may be disposed partially or entirely within the outer container 302 and may contain the elution column 308. In this embodiment, the column 308 is connected in series between the inlet needle 28 and the outlet needle 30, with the valve 15 in series between the tip of the outlet needle 30 and the elution column 308. Thus, fluid flowing from the inlet needle 28 passes through both the elution column 308 and the valve 15 before exiting the generator 22 via the outlet needle 30.

[0031] In operation, fluid inside the eluant source 24 is circulated through the inlet needle 28, through an eluant fluid passage 310 of the generator 22, through the elution column 308, through an eluate fluid passage 312 of the generator (which includes the valve 15), and out through the outlet needle 30 located at the eluate outlet end of the generator 22, into the eluate receptacle 26. As such, the fluid passage of this generator includes the inlet needle 28, the eluant fluid passage 310, the elution column 308, the eluate fluid passage 312, the valve 15, and the outlet needie 30. Fluid passages of other generators may include other appropriate components and/or different designs of the illustrated components. What is important is that the valve 15 is located within the fluid passage of the radioisotope generator. In some embodiments, it may be preferred to locate the vatve 15 toward the eluate output end of the generator (e.g., near or even in the output needle 30).

[0032] Continuing with operation of the generator 22, circulation of the eluant through the fluid passage of the generator washes out (e.g., extracts) a radioactive material, such as a radioisotope, from the elution column 308. For example, one embodiment of the generator 22 includes an interna! radiation shield (e.g., lead shell) that encloses a radioactive parent, such as molybdenum-99, affixed or otherwise coupled to the surface of beads of alumina or a resin exchange column, such as the elution column 308. Inside the generator 22, the parent molybdenum-99 decays into metastable technetium-99m. The daughter radioisotope (e.g., technetium-99m) is generally held in the column 308 less tightly than the parent radioisotope (e.g., molybdenum-99) within the generator 22. Accordingly, the daughter radioisotope can be extracted with a suitable eluant, such as an oxidant- free, physiologic saline solution. Upon collecting a desired amount (e.g., desired number of doses) of the daughter radioisotope within the eluate receptacle 26, the elution assembly 14 can be removed from the radioisotope elution system 10. As discussed in further detail below, the extracted daughter radioisotope can then, if desired, be combined with a tagging agent to diagnose or treat a patient (e.g., in a nuclear medicine facility). [0033] Although principles of the invention may be applied to any radioisotope elution system, the illustrated elution system 10 is configured to perform two types of elutions: a dry elution and a wet elution, examples of both of which are described below. To perform a dry elution, prior to the elution, the eluate receptacle 26 is substantially evacuated, and the eluant source 24 is filled with a volume of saline that generally corresponds to the desired volume of radioisotope solution. During a dry elution, the vacuum in the eluate receptacle 26 draws eluant from the eluant source 24, through the generator 22, and into the eluate receptacle 26. After substantially all of the eluant has been drawn from the eiuant source 24, a remaining vacuum in the eluate receptacle 26 draws air, or other non-eluant fluid, through the generator 22, thereby removing eluant that might otherwise remain in the generator 22, e.g., in the elution column 308, the valve 15, or the needles 28 and 30. Air or other appropriate fluids may flow into the eluant source 24 through the inlet vent needle 28 and into the generator 22 through the other inlet needle 28. The volume and pressure of the eluate receptacle 26 may be selected such that substantially all of the eluant is drawn out of the generator 22 by the end of an elution. in contrast, a wet elution potentially leaves eluant in the generator 22. The eluant source 24 is generally larger than the eluate receptacle 26, so an eluant source 24 may supply multiple elutions that refill the eluate receptacle 26 multiple times. Because the eluant source 24 and the generator 22 are not necessarily evacuated by the eluate receptacle 26, after a wet elution, residual eluant may remain in the generator 22.

[0034] To reduce the likelihood of residua! eluant leaking, the elution system 10 may include the valve 15. An exemplary position of the valve 15, in the presently described embodiment, is illustrated in FIG. 5, which is a top- perspective view of the elution system 10. In particular, the valve 15 is located at or near an eluate output end of the generator's fluid passage (e.g., coupled and in fluid communication with the outlet needle 30). As explained below, the valve 15 may be configured to automatically seal a passage in fluid communication with the outlet of the elution system 10 (e.g., the outlet needle 30). In some embodiments, the valve 15 is configured to automatically seal the passage in response to the removal of the eluate receptacle 26 and automatically unseal the passage in response to the presence of the eluate receptacle 26. Embodiments of the valve 15 are described below. [0035] FIG.7 illustrates the valve 15 in greater detail. In this embodiment, the valve 15 is a check valve (e.g., a one-way valve that opens in response to a difference in pressure across the valve above a threshold pressure and closes in response to a reduction in the pressure difference to below the threshold pressure). In this embodiment, the valve 15 includes the outlet needle 30, an upper body 34, a lower body 36, an upstream passage 38, and a resilient sealing member 40. The exterior of the valve 15 generally defines adjacent, circular, right- cylindrical volumes of differing aspect ratios that are generally concentric about a central axis 42. The needle 30 extends along the central axis 42 from a downstream side of the upper body 34. The downstream direction is indicated by arrow 44, which illustrates the overall direction of flow through the valve 15. The upstream passage 38 extends from an upstream side of the lower body 36. Additional details of the upper body 34 and lower body 36 are described below in reference to the cross-section a! views of FIGS. 11 and 12, after describing the resilient sealing member 40 in greater detail.

[0036] FIGS. 7-9 show the resilient sealing member 40. In this embodiment, the resilient sealing member 40 is a duckbill valve (e.g., a normally closed check valve having opposing faces that separate in response to fluid pressure across the valve). In certain embodiments, it may include other types of resilient sealing members configured to seal or otherwise obstruct a passage, or it may include sealing members biased against a passage by a resilient member, such as a spring, by gravity, or by some other force.

[0037] The illustrated resilient sealing member 40 may be injection molded or otherwise formed as a single body, and may include, or be made from, a resilient material, such as rubber or another elastomer. FIGS.8-10 illustrate the resilient sealing member 40 in a generally relaxed, or substantially unbiased, shape, which may correspond to the closed position, as explained below in reference to FIGS. 11 and 12. [0038] In this embodiment, the resilient sealing member 40 includes a base 46, a tip 48, faces 50 and 52, sides 54 and 56, and ribs 58 and 60. These features are generally reflectively symmetric about a plane of symmetry 62 in which the tip 48 generally lays, and which is generally perpendicular to the base 46. The illustrated tip 48 may have a generally curved shape or it may be angular. The tip 48 of this embodiment has a slot 64 defined in it that is generally within the plane of symmetry 62. The illustrated faces 50 and 52 define generally planar surfaces at an angle 66 relative to the plane of symmetry 62. In some embodiments, the angle 66 may be greater than, less than, or generally equal to 15°, 30°, 45°, 60°, or 75°. Together, the faces 50 and 52 and the sides 54 and 56 may define a volume generally corresponding to the intersection of a right, circular cylinder and a wedge with a vertex generally perpendicular to, and generally intersecting, a central axis of the right, circular cylinder. The ribs 58 and 60 may extend from the faces 50 and 52, respectively, and define a generally right prism shape. The sides 54 and 56 may be generally perpendicular to both the base 46 and the tip 48. The base 46 of this embodiment has an annulet, or generally circular fillet, shape that is generally concentric about the same axis as the sides 54 and 56 (e.g., the central axis 42 (FIG. 7)).

[0039] In operation, the resilient sealing member 40 may respond to a pressure difference between its interior (e.g., the space between the faces 50 and 52) and its exterior by opening or closing. For example, if the pressure in the interior of the resilient sealing member 40 is greater than the pressure at Its exterior by some threshold (e.g., greater than 0.05 psi, or 0.1 to 1 psi) the resilient sealing member 40 may respond by opening. As the resilient sealing member 40 opens, the base 46 may remain generally static, and the sides may deflect toward one another as indicated by arrows 68. Also during opening, the faces 50 and 52, and in particular, the portion of the faces 50 and 52 near the center of the tip 48, move away from one another as indicated by arrows 70. in some embodiments, slot 64 may extend along a substantial portion of the tip 48, and the faces 50 and 52 may move apart in opposite directions 70 more near the center of the tip 48 than near sides 54 and 56 to form an opening characterized by a shape similar to opposing, symmetric ogee arches.

[0040] FIGS. 11 and 12 illustrate other portions of the valve 15 in operation. Specifically, FIG. 11 illustrates the valve 15 in cross-section in the closed position, and FIG. 12 illustrates the valve 15 in cross-section in the open position. Prior to explaining its operation further, however, additional features of the valve 15 illustrated by these cross-sections are described.

[0041] In this embodiment, the upper body 34 (which may or may not include radiation shielding material) seals against the base 46 of the sealing member 40 and biases the base 46 against the lower body 36 (which may or may not include radiation shielding material) to form another seal. Together, these three components define an outer enclosure 72 and an inner enclosure 74, which are both generally isolated from the atmosphere except via needle 30 and the upstream passage 38, respectively. Further, the outer enclosure 72 is generally sealed from the inner enclosure 74 by the sealing member 40 when it is in the closed position. The shape of the outer enclosure 72 may generally correspond to the shape of the resilient sealing member 40 when it is in the open position. In some embodiments, the shape of the outer enclosure 72 may constrain the degree to which the resilient sealing member 40 opens, so that when the member 40 is open, a portion of the faces 50 and 52 of the resilient sealing member 40 contact the wall of the upper body 34 that defines part of the outer enclosure 72. Reducing this volume is believed to reduce the volume of eluate disposed downstream of the sealing member 40 after an elution. [0042] Referring to FIG. 12, the presently described valve 15 may be opened by placing the valve 15 in fluid communication with an interior 76 of the eluate receptacle 26. To this end, the eluate receptacle 26 is moved generally along the central axis 42 in direction 78, until and after the needle 30 pierces a septum 80 or the like (e.g., a rubber stopper). The interior 76 of the eluate receptacle 26 may be at sub-atmospheric pressure (e.g., a partial or near total vacuum). When fluid communication is achieved, pressure in the interior 76 of the eluate receptacle 26 equalizes with the pressure in the outer enclosure 72 of the valve 15 via the needle 30. As a result, in some embodiments, the pressure in the outer enclosure 72 decreases relative to the pressure in the inner enclosure 74. This pressure difference, in some embodiments, biases resilient sealing member 40 to the open position, with portions of the faces 50 and 52 near the slot 64 displaced away from one another. When the valve 15 opens, the pressure in the interior 76 of the eluate receptacle 26 may then partially equalize with the pressure in the inner enclosure 74 and the upstream passage 38, such that the receptacle 26 may draw eluate from the generator 22, as described above.

[0043] When the pressure in the interior 76 of the eluate receptacle 26 generally equalizes (e.g. drops below a threshold pressure for the resilient sealing member 40) the illustrated valve 15 closes. Without a pressure difference between the inner enclosure 74 and the outer enclosure 72, the faces 50 and 52 may relax and move toward one another, thereby closing the slot 64 at the tip 48, After the eluate receptacle 26 is removed, the outer enclosure 72 may return to atmospheric pressure, or near atmospheric pressure, and the resilient sealing member 40 may remain generally in the closed position.

[0044] In some embodiments, the valve 15 closes before the eluate receptacle 26 is removed. The flow of eluate 26 into the eluate receptacle 26 may raise its pressure such that the pressure drop across the valve 15 decreases below the threshold pressure, which may close the valve 15 before the eluate receptacle 26 is removed. [0045] Closing the valve 15 is believed to reduce the likelihood of residual eluate in the generator 22 escaping from the needle 30 after the eluate receptacle 26 is removed. Moreover, in this embodiment, because the valve 15 includes the needle 30, and because the resilient sealing member 40 is adjacent to the needle 30, the enclosed volume downstream from resilient sealing member 40 is relatively small, so the potential volume of uncontained eluate is also relatively smalt. Further, the illustrated valve 15 includes generally one moving part: the resilient sealing member 40. Having relatively few moving parts is believed reduce the cost and complexity of the valve 15 relative to other techniques for containing eluate.

[0046] Other embodiments may include other types of valves and, in particular, other types of check valves. For instance, the valve 15 may be a reed valve with a resilient, cantilevered sealing member biased against the downstream side of an aperture. In another example, the valve 15 may include a sealing member that is biased against an opening by a resilient member, such as a spring, or by gravity. In some embodiments, the valve 15 may include a ball check valve in which a ball is biased against an opening by a spring or gravity. The ball may be displaced by a pressure difference to open the valve, and the ball may be returned by the spring to close the valve. Certain embodiments may include a flapper check valve in which a sealing member is connected to a sprung- hinged gate that allows the sealing member to swing open and closed based on a pressure difference across the gate.

[0047] Although the valves 15 described above tend to seal the outlet of an elution system 10, other embodiments may sea! an inlet or both an inlet and an outlet. For instance, the valve 15 may be reversed with respect to the direction of fluid flow and placed between the eluant source 24 and the generator 22 to seal the inlet to the elution system 10.

[0048] FIG. 13 illustrates an example of a radioisotope solution dispensing process 82, which may be executed with an elution system described herein. The illustrated process 82 begins with receiving an eluate receptacle having a fluid pressure, as illustrated by block 84. This receiving may include piercing a rubber septum of the eluate receptacle with a needle to place an interior of the eluate receptacle in fluid communication with the generator. The fluid pressure within the interior of the eluate receptacle may initially be a sub-atmospheric or near vacuum pressure. Next, fluid pressure is applied to a check valve of the elution system to open the check valve, as illustrated by block 86. Applying the fluid pressure may include generally equalizing, or decreasing a difference in, pressure in the eluate receptacle and the pressure on an upstream side of the check valve. Opening the check valve may include deforming a resilient member or overcoming some force, such as gravity. Next, eluate flows through the check valve and into the eluate receptacle, as illustrated by block 88. This act may tend to change (e.g. raise) fluid pressure in the eluate receptacle. The process 82 further includes removing the eluate receptacle and stopping the application of fluid pressure to the check valve, as illustrated by block 90. In some embodiments, the fluid pressure is removed or dissipated after a volume of eluate, such as a desired number of doses, has flowed into the eluate receptacle, and the eluate receptacle may not necessarily be removed to remove the fluid pressure from the check valve. In response to removal, or substantial dissipation, of the fluid pressure, the check valve is closed, as illustrated by block 92. Closing the check valve may include biasing a sealing member against an opening with a resilient member, such as a spring or with gravity.

[0049] FiG. 14 is a flowchart illustrating an exemplary nuclear medicine process that uses a radioactive isotope dispensed or isolated by flowing eluate or eluant through the previously described valve 15. As illustrated, the process 162 begins by providing a radioactive isotope for nuclear medicine at block 164. For example, block 164 may include eluting technetium-99m from the generator 22 illustrated and described in detail above. At block 166, the process 162 proceeds by providing a tagging agent (e.g., an epitope or other appropriate biological directing moiety) adapted to target the radioisotope for a specific portion (e.g., an organ or tissue) of a patient. At block 168, the process 162 then proceeds by combining the radioactive isotope with the tagging agent to provide a radiopharmaceutical for nuclear medicine. In certain embodiments, the radioactive isotope may have natural tendencies to concentrate toward a particular organ or tissue and, thus, the radioactive isotope may be characterized as a radiopharmaceutical without adding any supplemental tagging agent. At block 170, the process 162 then may proceed by extracting one or more doses of the radiopharmaceutical into a syringe or another container, such as a container suitable for administering the radiopharmaceutical to a patient in a nuclear medicine facility or hospital. At block 172, the process 162 proceeds by injecting or generally administering a dose of the radiopharmaceutical into a patient. After a pre-selected time, the process 162 proceeds by detecting/imaging the radiopharmaceutical tagged to the patient's organ or tissue (block 174). For example, block 174 may include using a gamma camera or other radiographic imaging device to detect the radiopharmaceutical disposed on or in or bound to tissue of a brain, a heart, a liver, a tumor, a cancerous tissue, or various other organs or diseased tissue. [0050] FiG. 15 is a block diagram of an exemplary system 176 for providing a syringe having a radiopharmaceutical disposed therein for use in a nuclear medicine application. As illustrated, the system 176 includes the radioisotope elution system 10, which may include the valve 15 or execute the process 82 described above. The system 176 also includes a radiopharmaceutical production system 178, which functions to combine a radioisotope 180 (e.g., technetium-99m solution acquired through use of the radioisotope elution system 10) with a tagging agent 182. In some embodiment, this radiopharmaceutical production system 178 may refer to or include what are known in the art as "kits" (e.g., Technescan^® kit for preparation of a diagnostic radiopharmaceutical). Again, the tagging agent may include a variety of substances that are attracted to or targeted for a particular portion (e.g., organ, tissue, tumor, cancer, etc.) of the patient. As a result, the radiopharmaceutical production system 178 produces or may be utilized to produce a radiopharmaceutical including the radioisotope 180 and the tagging agent 182, as indicated by block 184. The illustrated system 176 may also include a radiopharmaceutical dispensing system 186, which facilitates extraction of the radiopharmaceutical into a vial or syringe 188. In certain embodiments, the various components and functions of the system 176 are disposed within a radiopharmacy, which prepares the syringe 188 of the radiopharmaceutical for use in a nuclear medicine application. For example, the syringe 188 may be prepared and delivered to a medical facility for use in diagnosis or treatment of a patient. [0051] FIG. 16 is a block diagram of an exemplary nuclear medicine imaging system 190 using the syringe 188 of radiopharmaceutical provided using the system 176 of FIG. 14. As illustrated, the nuclear medicine imagining system 190 includes a radiation detector 192 having a scintillator 194 and a photo detector 196. In response to radiation 198 emitted from a tagged organ within a patient 200, the scintillator 194 emits light that is sensed and converted to electronic signals by the photo detector 196. Although not illustrated, the imaging system 190 also can include a collimator to collimate the radiation 198 directed toward the radiation detector 192. The illustrated imaging system 190 also includes detector acquisition circuitry 202 and image processing circuitry 204. The detector acquisition circuitry 202 generally controls the acquisition of electronic signals from the radiation detector 192. The image processing circuitry 204 may be employed to process the electronic signals, execute examination protocols, and so forth. The illustrated imaging system 190 also includes a user interface 206 to facilitate user interaction with the image processing circuitry 204 and other components of the imaging system 190. As a result, the imaging system 190 produces an image 208 of the tagged organ within the patient 200. Again, the foregoing procedures and resulting image 208 directly benefit from the radiopharmaceutical produced by the elution systems 10.

[0052] While the invention may be susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and have been described in detail herein. However, it should be understood that the invention is not intended to be limited to the particular forms disclosed. Rather, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the following appended claims.

Claims

1. A radioisotope generator comprising: a fluid passage; radiation shielding disposed about at least a portion of the fluid passage; and a check valve in fluid communication with the fluid passage, wherein the check valve is configured to obstruct the fluid passage depending on a fluid pressure difference between an upstream side of the check valve and a downstream side of the check valve.

2. The generator of claim 1 , wherein the pressure difference is a predetermined pressure difference.

3. The generator of claim 2, wherein the pressure difference is greater than 0.05 psi.

4. The generator of any preceding claim, wherein the check valve comprises a resilient sealing member.

5. The generator of any preceding claim, further comprising a needle coupled and in fluid communication with the downstream side of the check valve.

6. The generator of claim 5, comprising an at least partially evacuated vial having an interior in fluid communication with the needle, wherein the check valve is biased in an open position.

7. The generator of any preceding claim, wherein the check valve is located at or near an eluate output end of the fluid passage.

8. The generator of any preceding claim, wherein the check valve is a duckbill valve.

9. The generator of claim 8, wherein the duckbill valve comprises an elastomer.

10. The generator of any of claims 8-9, wherein the duckbill valve comprises a slot disposed near an intersection of two faces that slope toward one another.

11. The generator of any of claims 8-10, wherein the duckbill valve comprises a ring-shaped base and a housing that biases the ring-shaped base.

12. The generator of any of claims 8-11 , wherein the duckbill valve comprises generally circular, right-cylindrical shaped sides.

13. The generator of any of claims 8-12, wherein the duckbill valve comprises ribs,

14. A method of operation for a radioisotope generator, the method comprising: automatically closing an output of a radioisotope generator in response to a change in a fluid pressure.

15. The method of claim 14, wherein automatically closing comprises unbiasing a resilient sealing member.

16. The method of claim 14 or 15, wherein the change in the fluid pressure is a decrease in a pressure difference across a check valve of the radioisotope generator below a threshold pressure of the check valve.

17. The method of claim 16, further comprising flowing eluate through the check valve and into an eluate receptacle.

18. The method of claim 16 or 17, wherein the check vaive is a duckbill valve.

19. The method of any of claims 14-18, wherein the change in the fluid pressure is a result of a radioisotope solution at least partially filling a vial in fluid communication with the output of the radioisotope generator.