Patent Number: 061570362
Section: description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention summarized above and defined by the enumerated claims may be better understood by referring to the following detailed description, which should be read in conjunction with the accompanying drawings. This detailed description of particular preferred embodiments, set out below to enable one to build and use particular implementations of the invention, is not intended to limit the enumerated claims, but to serve as a particular examples thereof. The particular examples set out below are the preferred specific implementations of an automated air over eluent radioisotope elution/concentration system and method, namely, one that automatically elutes rhenium-188 from a tungsten-188 adsorbed alumina column (W-188/Re-188) generator, concentrates the eluate to produce patient-grade sodium perrhenate solution and provides a self-contained, leak-proof, sealed concentration cartridge. The description also sets out below a preferred implementation of system for eluting multiple generators in series. The invention however, may also be applied to other types of radioisotope systems and equipment as well. FIG. 2 illustrates the primary components of one preferred embodiment of the present inventive elution/concentration system. In particular, a first gas over eluent delivery mechanism 30 is shown in a vertically downward orientation. In this embodiment, the mechanism 30 is a syringe, which includes three components, namely, a barrel 31 defining a hollow cavity for containing fluid consisting of a first predetermined volume of gas 36, typically filtered air, positioned over a first predetermined volume of eluent, or liquid, 37, a plunger 32 placed within the hollow cavity and an output feed 34 to permit the eluent 37 and then gas 36 to travel through the system. The eluent may be a sterile saline solution or other acceptable solution. A first pressure supplying source 38 supplies a downward force upon the plunger 32 which, in turn, forces the gas 36 and liquid 37 through the output feed 34 and into a radioisotope generator 50. In this embodiment, the source 38 is a simple weight having a mass, m1. A free weight, such as m1, is inherently a constant pressure source in that cannot supply a force to the plunger greater than the gravitational pull on it (as opposed to some motor-driven pumps, for example, that have the capacity to overdrive). This force limiting feature is very advantageous from a safety standpoint. In particular, in the event that a plug develops in any of the components or tubing of the system that cannot be overcome, or unplugged, by the force of the weight upon the fluid, the procedure will simply and safely come to a halt. However, it is understood that any conventional device for supplying a downward force upon the plunger is acceptable. For example, a compressed spring having a spring constant k, may supply a variable force upon the plunger. Alternatively, an electro-mechanical device such as a motor with torque (force) limiting properties, may safely supply the force. Following the path of the fluid, the entire volume of the liquid 37 then passes through the W-188/Re-188 generator 50 and washes off the Re-188 radioisotope adsorbed on the generator column. The gas 36 follows immediately behind the liquid 37 to purge the generator of substantially all liquid contained therein. The solution, now carrying the desired radioisotope to be concentrated and called the "eluate," passes through the first elution tube 52 and is transported into a single-use concentration cartridge subsystem 60 via a hypodermic needle 56 which punctures a rubber septum 64 that serves as an inlet to the cartridge 60. As the mass 38 continues to force the plunger 32 downwardly, the eluate (and gas) then passes through a set of "impurity traps" 66, 68 and 70. These traps may consist of any chemical, radioisotope, or physical filters that are appropriate for the removal of undesirable components from the eluate. In the presently shown embodiment, the impurity traps are silver halide precipitation columns that are commercially available under the trade name "Maxi Clean Ic-Ag" columns (Alltech, Inc., Deerfield, Ill.). These traps are used to remove the chloride anions from the eluate, which if permitted to pass, would interfere with the trapping of the rhenium anions in the radioisotope trap. The eluate then passes through a check valve 72, which permits flow only in the direction of the arrow, and then through a radioisotope trap 76 that, as its name denotes, chemically traps the desired radioisotope therein and permits the passage of the solution through an adjustable three-way valve 78 and into a waste container 80. It should be understood that the radioisotope trap 76 may be any device that can accomplish the function of trapping the desired radioisotope. In the present embodiment, the trap 76 is an anion exchange column for concentrating thereon the perrhenate anion (Accell Plus QMA.TM. anion column, from Waters, Inc. Milford, Mass.). This completes the first step in the elution system of the present invention. The second elution eluent volume is smaller than the first so that the isotope can be concentrated by the ratio of V1:V2; where V1 is the first elution volume and V2 is the second elution volume. Accordingly, the second, smaller gas over eluent delivery mechanism 40 provides the second stage elution procedure. In particular, the mechanism 40 is a syringe which stores a second measured volume of fluid containing a second measured volume of liquid 47 and a second volume of gas 46 positioned over the liquid 47. The syringe is comprised of a barrel 45, a plunger 42 and a output feed 44. A second pressure supplying source 48 is applied to the plunger 42 in order to force the second volume of fluid through the system as now described. It should be understood that, as described above with respect to the first delivery mechanism 30, the particular pressure supplying source 48 shown in FIG. 2 is a constant pressure mass, of weight w2, but may be any other acceptable pressure supplying source. Further, the liquid 47 is typically the same solution and the gas 46 is typically the same purified air as is used in the first mechanism. The liquid (then gas) passes through a tube 54 and into the concentration subsystem cartridge 60 through a rubber septum 74 via another hypodermic needle 58. The check valve 72 prevents the liquid and gas from flowing in the direction opposing the arrow, and thus is forced to flow through the QMA.TM. column 76. This time, the fresh eluent 47, since it contains chloride anions, "re-elutes" the perrhenate anion that is adsorbed on the column and combines with it as a sodium perrhenate solution that passes through tube 81, out of the cartridge 60 via the hypodermic needle 59, and into a beta-shielded product vial 90, or other suitable receptacle, via tube 94. As shown, a venting filter 92 is placed through the sealed vial opening to permit the gas to escape from the vial. For the experimental system designed by the present inventors, the preferred volume of fluid for the first syringe 30 is 20-30 ml of eluent and 30-50 ml of gas. The preferred volumes in the second syringe 40 is 2-10 ml of eluent and 2-5 ml of gas. However, it should be understood that these figures are illustrative only and could, and likely will, be altered, depending on the desired final concentration of radioisotope, the size of the components, the distance the fluids must travel, and other factors. Referring now to the inventive concentration subsystem 60, it is shown that all of the components necessary for concentrating an eluate is contained in this single-use, sealed cartridge. In the preferred embodiment, the cartridge is comprised of 3/8 inch plexiglass beta shielding on all sides 62 and includes a handle 63 for minimal operator handling. In this way, any undesirable parent radioisotopes, chloride anions, and eluate waste solution is completely contained within this cartridge. The cartridge can also be configured to allow simple assay of radioactive contaminants within the waste fluid and columns for quality control of the generator system. Thus, the set up for an elution procedure merely requires: (1) filling the two (or more) syringes with the proper quantity of fluid; and (2) the simple drop-in placement of the cartridge 60 within a lead shielding casing 61, causing the hypodermic needles 56, 58 and 59 to puncture the sealed rubber septums 64, 74 and 82. Further, when an elution/concentration operation is completed, the operator simply lifts the cartridge 60 out of the holder 61 via the handle and can dispose of the cartridge with minimal handling and minimal safety risk to the operator. In addition to operator safety, the cartridge system allows maintenance of a sterile and pyrogen-free environment over an extended time and many elutions. Turning now to FIG. 3, shown is a simple flow chart which describes a method employed by the present invention. After the system is set up, the first volume of gas over liquid (eluent) is forced through the generator in step 100 (the elution step). In step 102, the first volume of gas over liquid (now as eluate) is forced through the impurity traps and radioisotope trap (the concentration step). In step 104, this first volume of liquid is permitted to enter a waste container for disposal. At this point, the first elution procedure is completed and, in step 106 the three-way valve which is located adjacent the output of the radioisotope trap is switched from its initial position which permits flow from the radioisotope trap into the waste container to a second position which prevents flow from the radioisotope into the waste container but permits the flow to an output tube. This step may occur manually or, preferably, automatically via a sensor or limit switch which senses that the first elution is completed. At this point, the second elution commences in step 108. In particular, a second volume of gas over liquid (eluent) is forced through the radioisotope trap thereby "lifting" the perrhenate anions that are trapped within. Finally, in step 110 this sodium perrhenate solution exits the concentration/elution system and enters as patient grade radio isotope solution into a sterile product vial. FIG. 4 shows the novel gas over eluent delivery mechanism 120 being used advantageously to elute multiple radioisotope generators in series. In particular, the mechanism 120, loaded with liquid eluent 122 and a gas 124, is connected to the first radioisotope generator 130 via the generator's inlet 128. A plunger 126 forces first the eluent 122 and then the gas 124 through the generator 130 and exits at its outlet 134 as an eluate. The gas 124 continues to force the liquid into a second generator 136 having an inlet 138 and outlet 140, thereby eluting the radioisotope adsorbed on this generator 136 as well. The outlet 140 of this generator may be fed into subsequent generators that are connected in series. The last generator n 144 has an outlet 146 which produces the eluate to be further processed in processing box 148. In particular, the eluate may be further processed in a concentration subsystem 150 as described above with reference to FIGS. 2 and 3, and then collected in a collection vial 152. Alternatively, in procedures that do not require a second concentration and elution step, the eluate that is output from the generators may enter directly into the collection vial 152. It should be understood that this mechanism 120 may be used to advantageously elute two used generators 130 and 136 in series or more. The number of generators that can be eluted in series is limited, theoretically, only by the size of the delivery mechanism 120 and the volume of gas 124 preloaded therein. In particular, there must be sufficient gas in the mechanism to completely purge all of the generators (and a concentration subsystem 150, if employed) of liquid. Having thus described exemplary embodiments of the invention, it will be apparent that further alterations, modifications, and improvements will also occur to those skilled in the art. Further, it will be apparent that the present concentration system is not limited to use with a W-188/Re-188 generator. Systems that produce other radioisotopes can also be improved using the system and method described herein. Such alterations, modifications, and improvements, though not expressly described or mentioned above, are nonetheless intended and implied to be within the spirit and scope of the invention. Accordingly, the foregoing discussion is intended to be illustrative only; the invention is limited and defined only by the various following claims and equivalents thereto.