CN102971800B - Multigenerator nucleic elution process and managing device - Google Patents

Abstract

For according to the elution time table multiple generator elution system from multiple parent-daughter generator (110a-d) selective elutions, it consider supply data, demand data and these generators each in can activity calculate this timetable.

Description

Multigenerator nucleic elution process and managing device

Technical field

The present invention relates to radioisotope generator field. More specifically, the present invention is directed to multiple generator elution system (elutionsystem).

Background technology

The Mo-99 supply that fission produces is in nondeterministic statement. Only two reactors (Canada's NRU reactor and Pei Teng (Petten) HFR reactor) represent about 60-70% that the world of the Mo-99 that fission produces supplies. When any one off-line in these reactors (no matter being in order to what be ranked safeguards or for the maintenance of non-scheduled), result is actually to be reduced by nuclear medicine procedure to only requisite case. For manufacture fission Mo-99 all reactors just close to the end in they relevant work life-spans, currently only plan one replace reactor, be called Pallas pendant Teng replace. The diffusion of the highly enricked uranium (HEU) (target for the Mo-99 that fissions) in the additionally concerned hands falling into terrorist or rogue government. HEU is used for the device that makes nuclear arms.

Alternatively, using, based on the generator of gel, the Mo-99 that the neutron activation (n, ��) from natural molybdenum obtains, this neutron activation can carry out in any nuclear reactor include power reactor. Unfortunately, when with from no matter U-235(is HEU or low-enrichment uranium (LEU)) fission produce Mo-99 compared with time, from n, �� method produce Mo-99 tend to that there is low specific activity (specificactivity). Low specific activity means that Mo-99 must be placed at absorbing all sluggish molybdenums on very big alumina column, or becomes insoluble gel-in-matrix (matrix), and it reduces can the cumulative volume of eluting post (such as molybdic acid zirconium or molybdic acid titanium). Subsequently, it is desirable to big elution volume carrys out eluting Tc-99m daughter nuclide (daughternuclide) post, particularly when use alumina column. The whole issue that prior art fails to solve low specific activity and/or low activity generator runs into.

Nucl.Med.Comm., 25609-614(2004) discuss the needs (" cold external member (cold-kit) " being constituted and because economic cause often requires that higher concentration bigger radiation pharmacy) of the high radioactivity concentration obtaining Tc-99m from molybdic acid zirconium gel generator.

The open method for concentrating Tc-99m from the Mo-99 adsorbent on the post of alumina base of United States Patent (USP) 5,729,821. The multiple post of system requirements realizes the concentration of eluate (eluate). Because Tc-99m is by the ion exchange with the chloride ion in saline solution, eluting leaves principal post, so multiple post must be used. Cation (sodium) is then removed by secondary post (being halogenation money base in this case), and pertechnetate (pertechnetate) concentrates for forming sodium pertechnetate with saline solution eluting subsequently in three anion columns.The method requires to use ackd salt or weak acid by Tc-99m from parent nuclide (parentnuclide) Mo-99(such as, alumina column) separate and eluting, and using cation seperation column cation to be removed from eluting so that high technetium acid ion (pertechnetateion) can be concentrated on anion column.

Application radiation and isotope (AppliedRadiationandIsotopes) 66(2008) the open method extracting Tc-99m from the solution containing Mo-99 of 1814-1817. This is the operation of complexity, and it requires to use organic solvent (tetrabutyl ammonium bromide (tetrabutylammoniumbromide) solution in dichloromethane (methylenechloride)) extract and concentrate Tc-99m.

Application radiation and isotope 66(2008) 1295-1299 is openly as the method for the version of method above, and wherein low specific activity alumina base generator saline solution eluting removes Tc-99m. Eluate is concentrated on strong anion exchanger Dowex post. Tc-99m by with the tetrabutyl ammonium bromide eluant solution with dichloromethane be collect remove in bottle. Organic solvent removes by being vacuum-drawn against dry and restores for using together with cold external member with saline solution. The time that Tc-99m owing to preparing concentration requires, the method is unpractiaca.

United States Patent (USP) 6,157,036 is openly for the method for low specific activity ion-exchange type generator (i.e. aluminium oxide). System multiple posts that to be used in method similar to U.S. Patent number 5,729,821. It is intrinsic safer that the method uses malleation to replace safer negative pressure to move fluid-negative pressure (vacuum) for relating to the transfer of active material.

It would therefore be desirable to have manage the system of the growth of daughter nuclide for efficiency purpose. There is a need in the art for elution system, it minimizes waste and maximizes the use of the daughter nuclide produced by a series of generators. Need further exist for reducing the elution system of the spread risk of HEU. Having also needed to manifold external member (manifoldkit), it can be operated for the eluate from a series of generators is directed to receiving flask by automatization's actuating system.

Summary of the invention

In view of the needs of this area, the present invention provides multiple generator elution system, and it includes multiple parent-daughter core generator and control system, and this control system is for following the tracks of the growth of each activity in these parent-daughter core generators.

Control system receives the demand data of the requirement that instruction activity produces, and is configured to the generator selected from generator with the first eluate eluting, in order to provide the desired amount of daughter nuclide. Receiving unit and receive demand data, it at least includes the timetable of the amount of daughter nuclide to produce and the amount that produces this daughter nuclide. This reception unit can operate together with control system so that the daughter nuclide eluting from multiple generators that is ranked is met the demand represented by this demand data by control system. Reception is also supplied data by this reception unit.

The present invention also provides for evaporating column and collects generator daughter nuclide for the generator selected from multiple generators. This evaporating column comprises suitable post medium. Such as, when daughter nuclide is Tc-99m, evaporating column is preferably the daughter nuclide anion column from its eluting. Provide the collection container for receiving daughter nuclide from described evaporating column equally.

It addition, the present invention provides control system multiple generator elution system, it is followed the tracks of the growth of each activity in parent-daughter core generator and is ranked from generator eluting to meet the demand of the input of daughter nuclide.

The present invention may also provide the second eluant source and carrys out eluting post. Depending on application, this second eluant may differ from the first eluant or both are identical. It addition, using identical eluant to come in the embodiment of eluting generator and evaporating column, eluant can extract from single source. Alternatively, the source of the first eluant can be respectively supplied to each generator, rather than from common source. The present invention also provides for when the high purity waters such as such as water for injection provide for eluting generator from public reservoir, and this water can be additionally used in the parts rinsing elution system between eluting runs. It is also contemplated that can provide high-purity water source only for rinsing the purpose of the parts of multiple generator elution system.

Additionally, the present invention also provides for the method for operating multiple generator elution system, it coordinates the input demand data of daughter nuclide produced by generator, follow the tracks of in time generator each in available activity, and be ranked from generator eluting to meet this input demand of daughter nuclide.

Additionally, the present invention provides the external member of manifold system, it can be operated will be directed to detached dowel from the eluting in multiple parent-daughter generators by control system.

The problem that this invention address that the those skilled in the art of management and the generator operated in core pharmacy. Non-limiting purpose use Tc-99m/Mo-99 generator for the purpose of illustration, the present invention combines and concentrates daughter nuclide technetium [Tc-99m] the pertechnetate eluting from multigenerator unit, and extends the useful life longevity of decay or low activity generator. The present invention manages isotope " growth " with maximal efficiency and cost savings automatically together with from ERP system or the demand data that is manually entered. The present invention also allows for operator's simulation " what-if " scene, for instance when simulating short supply and unexpected increase in demand etc. It addition, after the present invention can be contained in radiation barrier thing, this screen deposits safely generator and the radioactive parts of all process. The present invention allows gamma gel base Mo-99 generator operationally more competitive compared with fission base generator, consequently facilitating the practicable alternative to the radiogenic Mo-99 by highly enricked uranium (HEU), and thus reduce the diffusion of nuclear bomb level material. Additionally, the present invention provides prescription to constitute data exchange to electronic health record.

The Mo-99 isotope used in Tc-99m/Mo-99 generator typically represents the 75% or more of the totle drilling cost of generator. Generator and isotope buy single expense item maximum typically. Mo-99 decays into Tc-99m, Tc-99m also with known index percent decay with known index percent. Typical generator comprises the activity of known quantity when delivery. When this generator eluting, remove Tc-99m and stay Mo-99 to continue to decay into Tc-99m. Accurately determine that the calculating that on generator, the amount of available Tc-99m requires is extremely complex at any given time, and be not easy to carry out. The present invention provides control system, and it comprises for easy and quickly perform the software of these calculating. This software is utilized to allow control system to select the efficient combination of generator for any given demand together with multiple generator elution system. It addition, history or real-time requirement can the person of being operated by be manually entered or by obtaining from the data link of enterprise resource planning.

Molybdic acid titanium " gel " base generator uses low-down specific activity Mo-99, and it causes less concentration and has the eluting of general gross activity content more less than industrial standard fission Mo-99 base generator.This multiple generator elution system of the present invention is got rid of these problems and is allowed gel base generator operationally more competitive than industrial standard fission base generator.

Accompanying drawing explanation

Fig. 1 is the cross sectional representation of the parent-daughter generator of prior art.

Fig. 2 describes the active decay curve of Mo-99/Tc-99m generator.

Fig. 3 is depicted in the decay curve of the Tc-99m after the continuous eluting of Tc-99m isotope ion in Mo-99/Tc-99m generator.

Fig. 4 describes the multiple generator elution system of gel base Mo-99 generator.

The replacing representation of the elution system of Fig. 5 depiction 4.

Fig. 6 describes the multiple generator elution system of alumina base Mo-99 generator.

The replacing representation of the elution system of Fig. 7 depiction 6.

Fig. 8 describes box base (cassette-based) manifold of the part of the multiple generator elution system as the present invention.

Fig. 9 is the flow chart of the method describing the present invention.

Figure 10 describes the screenshotss of the graphic user interface (GUI) of the present invention for providing information provision to the multiple generator elution system of the present invention.

Figure 11 describes the screenshotss of the GUI of the eluting management system for multiple generator elution system.

Detailed description of the invention

Present invention concentration is from the eluate of large volume eluting, for requiring that " the cold external member " of more high radioactivity concentration restores. In one embodiment, the present invention is provided to the system of concentration Tc-99m. The present invention can concentrate eluate in bigger radiopharmaceutical and realize workflow efficiency, and the QC especially for eluate tests, and gets rid of the time that the multiple generator of eluting consumes respectively. Use expired more fully it addition, the present invention allows to close on expired generator (it is because of low yield and thus the less radioactive concentration of eluate tends to not using) and realize cost savings. The present invention comprises software and mates demand and supply better, thus realizing cost savings and minimizing waste and loss. The present invention avoids the needs using organic solvent, thus getting rid of waste and the use of harmful organic solvent.

The present invention provides multiple generator elution system, and it uses multiple parent-daughter generators, follow the tracks of these generators each in the isotopic growth relationship of parent-daughter, and concentrate the output of these generators of eluting. By whole three solutions that combine in these concepts about low specific activity generator in the intrinsic problem applied and in service efficiency.

Multiple generator elution system is preferably enclosed in radiation shield shell, for instance plumbous wall hot cell etc. Although work is used for managing the eluting from single generator by the present invention, but manages multiple generator in a preferred embodiment. One embodiment of the present of invention utilizes many Mo-99 titanium/Tc-99m titanium [Mo-99] molybdate gel generator, and it utilizes the Mo-99 that the neutron activation from natural molybdenum (n, �� Mo-99) obtains. Although making with particular reference to the eluting managed from Mo-99/Tc-99m parent-daughter generator, the present invention contemplates that may be used without other kinds of generator comes eluting and other daughter isotopes or daughter nuclide.

Thus in one embodiment of the invention, the shell of lead screen comprises one or more Mo99/Tc99m generators. These generators link together via fluid path system, and it enables any combination of generator to be eluted on evaporating column or multiple post. When Tc-99m, this evaporating column is cathode column.The Tc99m eluting subsequently of concentration leaves this evaporating column to be ready for the radioactive concentration entrance receiving flask of the requirement of use in radiopharmaceutical. Control system selects the most efficient combination of generator based on demand, available supply and demand in the future.

Current and the demand in the future of the available supply of activeness and activeness can respectively from generator self be manually entered from radiopharmaceutical Enterprise Resources Plan (ERP) system or be transferred into electronically to receive unit and metering-in control system. Such as, can electronically read from the label (such as bar code etc.) generator from the data of generator self transmission or scan. The calibration data of generator can be included about such data (also referred to as ' supply data ') of generator, it is provided that date and activity both. Additionally, it is contemplated that supply data include the time and date of time and date that generator may be used in and the deviation of the first eluting. Similarly, can manually or electrically input control system including the demand data of the activity of requirement and the time from the such activity of system requirements. And/or it is electronically entered it is contemplated by the invention that configuration data receives unit for the artificial of demand data.

Use supply data, the activity that control system can preferably can use in each generator to arrange interval (such as every 30 minutes) to calculate, and display it to operator. Demand data preferably similarly shows on the interval identical with supply data. Control system includes computer to calculate best fit elution curve or timetable, for select in available generator which by preset time eluting meet demand data with possible most efficient way, thus maximizing the useful life longevity of each generator and minimizing waste. The preferably sequencing of control system carries out the generalized reduced gradient Algorithm Analysis of the activity level of demand data and multiple generator to determine that suitable time of eluent table is for minimizing waste. Alternatively, it is contemplated by the invention that control system program to run the simulation of the various elution time tables from multiple generators, and the elution time table causing the daughter nuclide of minimum to be wasted when meeting demand data is selected. This elution time table also will provide for operator.

Preferably, elution time table be shown on GUI to provide, it is given operator and is ranked the option that different generators makes for the eluting in preset time the optimization elution time table of calculating invalid by replacement. When operator determines amendment elution time table, control system will recalculate elution time table and shows being ranked the time of active availability that each generator updates in time and each eluting from generator. If the elution time table updated is satisfied for operator, would be complying to the eluting instruction generator for selecting according to timetable eluting. So, the present invention provides ' operator is in the loop ' option to monitor and manage the eluting from generator, and allows operator to make the timetable of calculating invalid. Alternatively, the present invention is operable to intervene without operator and such that it is able to automatically carry out being ranked eluting without operator's input, thus make operator free and turn to other pharmacy responsibilities.

Eluting instruction will be used for the eluting of the generator that Electronic Control selects. When eluting generator, renewal growth is calculated and updates elution time table (if necessary) by control system.It is contemplated by the invention that operator or system will carry out the actually eluted step of generator confirming to select.

What use in filling elution time table calculates the known constant such as the mark by preferably considering eluting available in such as parent nuclide half-life and decay equation, daughter nuclide half-life and decay equation, eluting output efficiency and parent nuclide decay. It addition, control the time expiration of the system equilibrium equation by consideration parent-daughter and generator. Most of generators have 2 week life (this be pharmacy expire require), if but parent isotope has long half-lift (such as, Sr-90/Y-90) then it can be much longer.

The present invention provides the advantage in both many technology and economy. The present invention is it is thus possible to carry out as the concentrator each eluting being run to the activity from the generator eluting selected. This not only allows for the efficient utilization of generator, and it also allows for closing on expired generator and still can combination with one another utilize, this is because their active concentration is together. Automation mechanized operation can reduce pharmacy office worker and be exposed to dosage. Realize labor efficiency equally. Such as, if four generator eluting respectively, then four distinct quality control tests are required. The present invention allows the eluting of concentration is only carried out single quality control test by concentrating individual eluting, it is allowed to more activity is retained in receiving flask for Clinical practice.

The use of gel generator is the invention enables to become the option of viable commercial, although they are for the fission relatively low by contrast specific activity of generator. The multiple generator elution system (MGES) of the present invention is intended to get rid of the inferior position of gel base generator system discussed above. It addition, using of gel generator improves the management of isotope supply during by the cut-off of conventional source or shortage.

System preferably includes the shielding area of two or more gel generator accommodating. These generators connect and separate valve manifold, and it can by controlling generator that Systematic selection selects at reasonable time eluting with the satisfied demand planned. Tc-99m by make eluant by select one or more generators and eluting. Tc-99m collects on aluminium oxide evaporating column. When completing from the collection of generator, control system this evaporating column of eluent and enter the receiving flask of industrial standard shielding. This eluant can extract eluting generator from currently used reservoir or from individual bottle of saline solution.

All fluid paths, evaporating column and receiving flask equipment are preferably shielded by hot cell and provide the radiological protection to operator. The shielding of individual component can also provide in radiation shield hot cell.

The various methods of concentration Tc-99m eluting are described. For determining that the calculating of the growth relationship of parent daughter isotope is it is well known that but owing to complexity is rarely needed. N, �� Mo-99 use in gel generator system and other generator systems is also known. In these concepts whole three are joined together into individual system by the present invention, its management supply data of multiple generators, Useful active and demand data, and overcome about low specific activity generator in the intrinsic problem applied and in service efficiency.

The present invention will work together with molybdic acid zirconium or molybdic acid titanium gel generator system. Utilizing amendment, the present invention (as described in detail) will work with alumina base system equally together. To work together with alumina base system, therefore to would be required to other post and fluid path.

Have turned out the concept of molybdic acid titanium gel Generator Design. After the natural molybdenum of this gel irradiation, irradiation produces. The method set up includes the preformed gel of irradiation or molybdenum trioxide. Irradiation metal provides output, safety and treatment effeciency advantage.

Referring now to Fig. 1, prior art and the parent-daughter generator 110 of the multiple generator elution system of including the present invention in include long-lived parents-nucleic, it decays into more short-life daughter nuclide. Because parent and daughter nuclide are not isotopes, chemical isolation daughter nuclide is possible. Guide the eluant post by comprising parent and daughter nuclide, but only take away daughter nuclide as the eluate from this post. After eluting, parent nuclide (is retained in generator) the fresh supply that decay provides daughter nuclide. Generator is it is thus possible to provide the fresh supply of daughter nuclide as required until exhausting parent active.

Generator 110 includes the generation body 112 formed with radiation shielding materials such as such as lead. Body 112 is occurred to limit the post chamber 114 comprising the post 116 keeping parent nuclide. Body 112 is occurred to limit elongated eluant passage 118 and elongated eluate passage 120, its fluid communication extension between post chamber 114 and eluant chamber 122 and collecting chamber 124 respectively. Post 116 comprises medium 126, and parent nuclide is in connection, but daughter nuclide therein can from its eluting. Eluant chamber 122 supports eluant bottle 130 and collecting chamber 124 supports receiving flask 132 therein. Eluant conduit 134 is in fluid communication extension to carry eluant to enter post 116 in bottle 130 between eluant bottle 130 and post 116. Often holding, eluant conduit 134 terminates respectively in elongated spicule 125a and the 125b of the barrier film for piercing through bottle 130 and post 116. Eluate conduit 136 extends to receiving flask 132 from post 116 eluate is delivered into bottle 132 from post 116. Often holding, eluate conduit 136 terminates respectively in elongated spicule 129a and the 129b of the barrier film for piercing through bottle 132 and post 116. Typically, receiving flask 132 is evacuated vial so that eluant fluid is drawn into wherein by post 116 by the low pressure in this bottle from eluant bottle 130. Independent air inlet conduit 140 is in fluid communication extension between eluant bottle 116 and air entry filter 142, in order to auxiliary eluant empties from eluant bottle 130. Typically, receiving flask 132 is contained in the radiation shield 144 of its own and makes screen 144 can be taken off the eluate of collection with it to pharmacists for processing further from removing of collecting chamber 124 by carrying the receiving flask 132 being now filled with.

In one embodiment, post 116 comprises Mo-99, and it decays into Tc-99m, and wherein acidic alumina is as adsorbent. Then post 116 will be acidic alumina column, although being used as other kinds of post as previously described. It is contemplated by the invention that comprise multiple generator 110. As will be shown below, it is still further contemplated that provide, each generator conduit towards public receiving flask is substituted receiving flask. It addition, it is contemplated by the invention that replace each generator with the eluant bottle 130 of its own, and eluant common source can be provided, it can be directed to any and whole generator in generator as requested. Such as, when post 116 is the acidic alumina column with Mo-99, eluant bottle 130 can provide source of saline solution to be used for from this post eluting Tc-99m nucleic.Alternatively, for instance for gel generator, eluant can be provided as the water source injected.

It is contemplated by the invention that the generator used by the present invention fission or n, �� generator. Such as, the TechneLite sold by LantheusMedicalImaging, 331TrebleCoveRd., N.Billerica, MA01862, USA can be used(technetium Tc99m generator). This TechneLite generator is considered the generator of dry type generator, and it means that it has the external source of saline solution and carrys out elution system. Most of generators tend to adopting this form. Similar to other fission base generators, this TechneLite generator is easy to the storage of Mo-99 and being subsequently isolated of daughter isotope Tc-99m based on acidic alumina column. Similarly, generator 110 can include by the Ultra-Technekow DTE(technetium Tc-99m generator of CovidenMallinckrodtInc., 2703WagnerPlace, MarylandHeights, MO63043, USA sale). This Ultra-Technekow and TechneLite unit is closely similar. Additionally alternatively, Drytec(technetium Tc-99m generator) can be used in conjunction with. Drytec generator is sold by GEHealthcare, TheGroveCentre, WhiteLionRoad, LittleChalfont, BuckinghamshireHP79LL, UK, and similar to other fission generators listed above.

Additionally, generator 110 n, �� or gel generator. One gel generator is by India government atomic energy ministry, BRIT/BARCVashiComplex, Sector-20Vashi, NaviMumbai-400705, the Tc-99m-Geltech generator that India sells. This Geltech generator of 99mTc is dual column system, and it comprises main molybdic acid zirconium-99Mo gel column and secondarily purified acidic alumina column. Although the generator of these types is structurally different from fission type generator, still adopts similar mode to operate and use saliferous eluant to produce sodium pertechnetate. Although gel generator is not really chromatographic, the also fluid leading to generator and the term ' eluate ' of describing used herein is described, by also used herein, the fluid leaving gel generator together with daughter nuclide by term ' eluant '.

Fig. 2 describes the active decay curve of Mo-99/Tc-99m generator. Fig. 3 illustrates that how in time Useful active decay until reaching the otiose point of generator. Fig. 3 is also depicted in the decay curve of the Tc-99m after the continuous eluting of Tc99m isotope ion in Mo-99/Tc-99m generator. And line A describes the overall decay of parent nuclide Mo-99, line B-D describes the growth of daughter nuclide Tc-99m, until daughter nuclide makes do not have remaining near maximum value in the post of generator at this time eluting. Parent nuclide decays into daughter nuclide by continuing, and therefore illustrates the increase in the Useful active of daughter nuclide in time. Equation 1 is equilibrium equation, its Mo-99 active A existed when describing the eluting before known⁰ ₁Time, the theory T c-99m activity (A that any time after eluting before exists in generator₂).

Equation (1)

Wherein ��₁It is the decay constant of Mo-99, and ��₂It it is the decay constant of Tc-99m. The active availability of each calculating in activity demand and generator is connected by the present invention.

Fig. 4 describes the multiple generator elution system 200 of the present invention. Multiple generator elution system 200 comprises multiple generator 110.These generators 110 are preferably connected to include the manifold (not shown) of valve and conduit so that the individual generator that the individual valve in these valves is corresponding with these generators becomes selectable fluid communication. Preferably, this manifold is connected to low pressure or vacuum source, for lifting eluant by system 300. Generator eluate output is directed to evaporating column 212 by this manifold. The generator that eluant is directed to generator 110 to select from the first eluant source 214, and is all directed to post 212 from the gained eluate of the generator of these selections. Daughter nuclide from generator is trapped in wherein by evaporating column 212. The second eluant from the second eluant source 216 is conducted through evaporating column 212 and daughter nuclide is eluted into receiving flask 218. Generator 110, post 212, eluant source 214 and 216 and receiving flask be preferably placed in the chamber 224 in radiation shield hot cell 222 to limit the exposure of operator.

System 200 includes control system 226 and receives unit 228. Reception unit 228 and control system 226 can be provided as the part of single computer systems. Receiving unit 228 and receive supply data and demand data, control system 226 can use them to generate the elution time table of generator 110, as will be Fig. 9-12 described. These supply data allow to calculate each available live vol that may be from generator 110 based on calibration data, it includes known initial activity and date, generator may be used in time and date and the time and date of the first eluting deviation. This demand data relates to the live vol and when of requirement. This demand data can be input to reception unit 328 from ERP modules 231 such as such as SAP or Slimline automatically, or it can be input manually into reception unit 228. Control system 226 is preferably determined by which generator of eluting and when calculates elution time table demand data to be mated with Useful active, in order to maximizes the daughter nuclide of eluting and has the waste of minimum. Then preferably download instruction to the actuating system 235 being positioned at hot cell 222 is used for implementing eluting by control system 226. It is still further contemplated that control system 226 can alternatively be provided in hot cell 222, with the actuating system 235 single computerized system separately or as the function carrying out both.

By illustrative not limiting, in the configuration, generator 110 is Mo99/Tc99m generator ([99Mo] molybdic acid titanium) gel generator. First eluant source 214 preferably provides weak acid as being used for from first eluant of generator eluting daughter nuclide Tc-99m, although such as can also be used for eluting gel generator for high purity waters such as the sterilized water injected. Evaporating column 212 includes alumina adsorbant and catches from the pertechnetate in the eluate of generator 110. Second eluant source 216 provides saline solution be used for from post 212 eluting sodium pertechnetate and collect receiving flask 218. Then sodium pertechnetate can use for labelled isotope-tracer in clinical diagnosis together with cold external member.

Utilize the present invention, can any combination of eluting generator, and collect in post 212 from the activity of the generator of eluting. Final radioactive concentration is determined by the eluting of evaporating column 212, its can in very little volume eluting. It addition, because activity can be collected from multiple generators and concentration, so generator can use continuously until expiring.

Referring now to Fig. 5, it is shown that the replacement of multiple generator elution system 200 presents.In fig. 5, it is shown that five the gel generator 110a-e being connected with valve manifold 250. Manifold 250 is preferably based at the FASTlab sold by GEHealthcare, Liege, BE^TMThe linear plug manifold arranged used in box. Manifold 250 includes 16 3 logical/3 position plug valve 1-17. Each in valve 1-17 includes contiguous manifold valve and is pointed to three open ports that corresponding Rule (luer) between is opened. Each valve includes rotatable plug, and it makes any two fluid communication with each other in the port that these three associates be fluidly isolated the 3rd port simultaneously. It is still further contemplated that plug can include T-shaped inner passage wherein, to allow also to whole three ports be positioned to stride across valve fluid connection, but such embodiment will provide for dead space, it may require that other rinsing to prevent the generation of pollution between continuous fluid flowing. Manifold 250 farther includes the first and second socket connectors 18 and 19 in its opposite end, each respectively limits vacuum ports 18a and 19a. Plug and the conduit described below of manifold 250 and valve 1-17 are preferably formed with polymeric material, for instance PP, PE, polysulfones, Polyetherimide (Ultem) or polyether-ether-ketone (Peek). As figure 8 illustrates, although the actual number of valve is the adjustable needs meeting user, manifold preferably includes 25 3 logical/3 position plug valves. The valve not used can make their Rule connection be covered by Luer coupler simply, and their plug provides fluid communication to the flowing between adjacent valve.

Each in the connection at valve place described herein makes in the port limited by its luer connector. As shown in fig. 5, valve 1 supports filtering outlet 251 in its junction, Rule. Valve 2 is connected to the first eluant source 214 by slender conduit 252. First eluant source 214 provides eluant to be used for from generator 110a-e eluting daughter nuclide. First eluant source 214 is preferably also connected with filtering outlet 233 communication to be assisted eluant to pass through conduit 252 to flow out towards valve 2. Valve 3 is connected to the second manifold 256 by slender conduit 254, it is provided that to the open connection of the eluant passage 118 of generator 110a-e. That is, although the present invention is also contemplated within each generator as illustrated in fig. 1 and can have an eluant source of its own, but the present invention preferably provides each in eluting generator of the single source of eluant. The eluate passage 120 of generator 110a-e connects back to manifold 250 respectively through slender pipeline 260a-e. Conduit 260a-e extends respectively between the corresponding eluate passage 120 of generator 110a-e to valve 4-8.

Valve 9 is connected to the input port of evaporating column 212 by slender pipeline 262 so that the eluate from generator is directed to post 212. Valve 10 is connected to the second eluant source 216 by slender conduit 264. Second eluant source 216 provides eluant from post 212 eluting daughter nuclide. Second eluant source 216 is preferably connected to filtering outlet 263 also fluidly coupledly and assists the second eluant to be flowed out towards valve 9 by conduit 256. Valve 11 and 12 is covered by Luer coupler, and their plug orientation provides the fluid flowing by it between valve 10 and 13. Valve 13 is connected to the input port 268 of receiving flask 218 by slender conduit 266, enabling guide products stream therein. Valve 14 is connected to the input port 272 of waste material bottle 219 by slender conduit 270.Valve 15 is connected to the output port of post 212 so that post 212 is preferably directly connected to valve 15. Valve 16 is connected the output port 275 of waste material bottle 215 by slender conduit 274. Valve 17 is connected to the output port 278 of receiving flask 218 by slender conduit 276.

Example eluting be will now be described. Having calculated elution time table, its requirement is activity eluted from generator 110a and 110c. By applying vacuum (that is, enough low pressure) at port 19a, the first eluant will extract from the first source 214. Arrange valve 1-17 to make the first eluant flow through valve 2 and 3 and conduit 254 to enter manifold 256. First, arranging valve 5-8 allows the eluate from generator 110a to flow through conduit 260a to valve 9. Valve 9 guides this eluate to flow through the conduit 262 input port to post 212. Eluate will be extracted by valve 15 to valve 14 from post 212 and enter waste material bottle 219. The volume of waste material bottle 219 will enough collect the whole of the liquid carried from post 212. Then the plug of changeover valve 4 isolates generator 110a, and the plug of valve 6 rotates and makes the first eluant will be drawn into generator 110c from the second manifold 256. Then eluate from generator 110c guides by valve 6-8 to valve 9. Valve 9 guides eluate to flow through the conduit 262 input port to post 212. Eluate will be extracted by valve 15 to valve 14 from post 212 and enter waste material bottle 219. From generator 110a and 110c daughter nuclide thus collect in evaporating column 212.

In order to from post 212 eluting daughter nuclide, the second eluant from source 264 by conduit 264 and is guided towards valve 9 by valve 10 by being arranged under the suction of port 19a. Second eluant extracts and passes through the input port of post 212 and by post 212 by conduit 262. When leaving post 212 and entering valve 15, post 212 eluate will comprise daughter nuclide and be used for allotting entrance receiving flask 218. This eluate is directed to valve 13 and enters bottle 218 by conduit 266, from port 19a be aspirated through valve 17 and conduit 276 applies. Then bottle 218 can be removed or offer daughter nuclide of releasing is for being processed further by pharmacists. Subsequently from generator allot thus the identical receiving flask of bootable entrance or additionally with is combined from the eluate that do not use allotted before because control system 226 it be used for from the calculating of generator 110a-e allocation, included any remaining activity to meet the requirement of demand data.

Manifold 250 is preferably formed and is attached to actuating system 235, and it engages and arranges the orientation of plug of valve and provide low-pressure suction or vacuum for drawing fluid through this manifold and entering bottle. Actuating system 235 includes rotatable arm, each in the plug of its engagement valve 1-17 and can be placed in desired orientation by each in elution action. Also including a pair sleeve pipe according to actuating system 235 of the present invention, wherein in each joint port 18a and 19a becomes fluid-tight to connect provides low pressure or vacuum source to manifold 250. Preferably, manifold 250 is attachable to FASTlab^TM(being sold by GEHealthcare, Liege, BE) synthesizer, its sequencing operates valve and applies vacuum. Because FASTlab synthesizer has been designed for operating in the environment of hot cell, so it is ideally suited as the actuating device of system 200. Actuating system 235 is by controlling system 226 according to the elution time table commander's action calculated.

The multiple generator elution system 300 of alumina base Mo99 generator 110 is described in Fig. 6 and 7. Multiple generator elution system 300 comprises multiple generator 110. In this embodiment, these generators 110 are Mo99/Tc99m aluminium oxide generator (that is, comprising aluminium oxide in the post of generator). Generator 110 is preferably connected to include the manifold (not shown) of valve and conduit so that the individual generator that the individual valve in these valves is corresponding with these generators becomes selectable fluid communication. Generator eluate output is directed to cation seperation column 315 by this manifold. Generator eluate flows through this cation seperation column 315 subsequently into evaporating column 312. Preferably, this manifold is connected to vacuum source for lifting eluant by system 300. This cation seperation column is not used in bottles up daughter nuclide and comprises suitable medium for removing competing ions, and it adversely disturbs evaporating column. Thus, the generator that eluant is directed to generator 110 to select from the first eluant source 314 within the system 300, and from the gained eluate of the generator of these selections entirely through post 315 and to post 312. Daughter nuclide from generator is trapped in wherein by evaporating column 312. The second eluant from the second eluant source 316 is conducted through evaporating column 312 and daughter nuclide is eluted into receiving flask 318. Generator 110, post 312, eluant source 314 and 316 and receiving flask be preferably placed in the chamber 324 in radiation shield hot cell 322 to limit the exposure of operator.

System 300 includes control system 326 and receives unit 328. Reception unit 328 and control system 326 can be provided as the part of single computer systems. Receiving unit 328 and receive supply data and demand data, control system 226 can use them to generate the elution time table of generator 110, as will be Fig. 9 and 10 described. These supply data allow based on calibration data calculate can each live vol obtained from generator 110, it includes known initial activity and date, generator may be used in time and date and the time and date of the first eluting deviation. This demand data relates to the live vol and when of requirement. This demand data can be input to reception unit 328 from electronics ERP modules 331 such as such as SAP or Slimline automatically, or it can be input manually into reception unit 328 by operator. Control system 326 is preferably determined by which generator of eluting and when calculates elution time table demand data to be mated with Useful active, in order to maximizes the daughter nuclide of eluting and has the waste of minimum. Then preferably download instruction to the actuating system 335 being positioned at hot cell 322 is used for implementing eluting by control system 326. It is still further contemplated that control system 326 can alternatively be provided in hot cell 322, with the actuating system 335 single computerized system separately or as the function carrying out both.

In the configuration, the first eluant source 314 preferably provides ackd salt or weak acid (typically saline solution) the first eluant as being used for from generator eluting daughter nuclide Tc-99m. Because the first eluant is saline solution, so cation seperation column 315 is initially used for removing sodium ion to allow to be concentrated on evaporating column 312. Evaporating column 312 includes alumina adsorbant and catches from the pertechnetate in the eluate of generator 110. Second eluant source 316 provides saline solution be used for from post 312 eluting sodium pertechnetate and collect receiving flask 318.Then sodium pertechnetate can use for labelled isotope-tracer in clinical diagnosis together with cold external member.

Utilize the present invention, can any combination of eluting generator, and and collect in post 312 from the activity of the generator of eluting by post 315. Twin columns method allows to utilize the odds for effectiveness of the concentrator system of the present invention based on the generator of fission Mo-99 and aluminum oxide technology. Final radioactive concentration is determined by the eluting of evaporating column 312, its can in very little volume eluting. It addition, because activity can be collected from multiple generators and concentration, so generator can use continuously until expiring.

Referring now to Fig. 7, it is shown that the replacement of multiple generator elution system 300 presents. In FIG. 7, it is shown that five the gel generator 110a-e being connected with valve manifold 350. Manifold 350 is preferably based at the FASTlab sold by GEHealthcare, Liege, BE^TMThe linear plug manifold arranged used in box. Manifold 350 includes 16 3 logical/3 position plug valve 1-17. Each in valve 1-17 includes contiguous manifold valve and is pointed to three open ports that corresponding Rule thereon is opened, and this Rule port is between other relative ports. Each valve includes rotatable plug, and it makes any two fluid communication with each other in the port that these three associates be fluidly isolated the 3rd port simultaneously. It is still further contemplated that plug can include T-shaped inner passage wherein, to allow also to whole three ports be positioned to stride across valve fluid connection, but such embodiment will provide for dead space, it may require that other rinsing to prevent the generation of pollution between continuous fluid flowing. Manifold 350 farther includes the first and second socket connectors 18 and 19 in its opposite end, each respectively limits vacuum ports 18a and 19a. Plug and the conduit described below of manifold 350 and valve 1-17 are preferably formed with polymeric material, for instance PP, PE, polysulfones, Polyetherimide or polyether-ether-ketone. As figure 8 illustrates, although the actual number of valve is the adjustable needs meeting user, but manifold preferably includes 25 3 logical/3 position plug valves. The valve not used can make their Rule connection be covered by Luer coupler simply, and their plug provides fluid communication to the flowing between adjacent valve.

Each port, Rule limited by its luer connector that is connected in the connection at valve place described herein is made. As figure 8 illustrates, valve 1 supports filtering outlet 351 in its junction, Rule. Valve 2 is connected to the first eluant source 314 by slender conduit 352. First eluant source 314 provides eluant to be used for from generator 110a-e eluting daughter nuclide. First eluant source 314 is preferably also connected with filtering outlet 333 communication to be assisted eluant to pass through conduit 352 to flow out towards valve 2. Valve 3 is connected to the second manifold 356 by slender conduit 354, it is provided that to the open connection of the eluant passage 118 of generator 110a-e. That is, although the present invention is also contemplated within each generator as illustrated in fig. 1 and can have the eluant source of its own, the present invention preferably provides each in eluting generator of the single source of eluant. The eluate passage 120 of generator 110a-e connects back to manifold 350 respectively through slender pipeline 360a-e. Conduit 360a-e extends respectively between the corresponding eluate passage 120 of generator 110a-e to valve 4-8.

Valve 9 is connected to the input port of cation seperation column 315 by slender pipeline 362. Cation seperation column 315 is served and is always removed competing ions from the eluate of generator before concentration. Valve 10 is connected to the second eluant source 316 by slender conduit 364. Second eluant source 316 provides eluant from post 312 eluting daughter nuclide. Second eluant source 316 is also preferably fluidly coupled to filtering outlet 363 and assists the second eluant to be flowed out towards valve 9 by conduit 362. Valve 11 is connected to the output port of cation seperation column 315. Valve 12 is connected to the input port of evaporating column 312 by slender conduit 365.

Valve 13 is connected to the input port 372 of waste material bottle 319 by slender conduit 370. Valve 14 is connected to the input port 368 of receiving flask 318 by slender conduit 366, so as to guide products stream therein. Valve 15 is connected to the output port of post 312 so that post 312 is preferably directly connected to valve 15. Valve 16 is connected the output port 375 of waste material bottle 315 by slender conduit 374. Valve 17 is connected to the output port 378 of receiving flask 318 by slender conduit 376.

Example eluting be will now be described. Having calculated elution time table, its requirement is activity eluted from generator 110a and 110c. By applying vacuum (that is, enough low pressure) at port 19a, the first eluant will be extracted from the first source 314. Arrange valve 1-17 to make the first eluant flow through valve 2 and 3 and conduit 354 to enter manifold 356. First, arranging valve 5-8 allows the eluate from generator 110a to flow through conduit 360a to valve 9. Valve 9 guides this eluate to flow through the conduit 362 input port to cation seperation column 315. Eluate will be extracted by valve 12 from post 315 and entered slender conduit 265 and enter the ingress port of evaporating column 312. Continuation is extracted and down to valve 13 and is entered waste material bottle 319 by valve 15 by post 312 by waste material. The volume of waste material bottle 319 will enough collect the whole of the liquid carried from post 315. Then the plug of changeover valve 4 isolates generator 110a, and the plug of changeover valve 6 makes the first eluant will be drawn into generator 110c from the second manifold 356. Then eluate from generator 110c guides by valve 6-8 to valve 9. Valve 9 guides eluate to flow through the conduit 362 input port to post 315. Eluate will be extracted by valve 12 from post 315 and entered slender conduit 265 and enter the ingress port of evaporating column 312. Continuation is extracted and down to valve 13 and is entered waste material bottle 319 by valve 15 by post 312 by waste material. From generator 110a and 110c daughter nuclide thus collect in evaporating column 312.

In order to from post 312 eluting daughter nuclide, valve 10 by lower for the suction being arranged in port 19a the second eluant guided from source 316 by conduit 364 and towards valve 12. Second eluant extracts and passes through the input port of post 312 and by post 312 by conduit 365. When leaving post 312 and entering valve 115, post 312 eluate will comprise daughter nuclide and be used for allotting entrance receiving flask 318. This eluate is directed to valve 14 and enters bottle 318 by conduit 366, from port 19a be aspirated through valve 17 and conduit 376 applies. Then bottle 318 can be removed or offer daughter nuclide of releasing is for being processed further by pharmacists or technical staff. Subsequently from generator allot thus the identical receiving flask of bootable entrance or additionally with is combined from the eluate that do not use allotted before because control system 326 it be used for from the calculating of generator 110a-e allocation, included any remaining activity to meet the requirement of demand data.

Manifold 350 is formed and is attached to actuating system 335, and it engages and arranges the orientation of plug of valve and provide low-pressure suction or vacuum for drawing fluid through this manifold and entering bottle. Actuating system 335 includes rotatable arm, each in the plug of its engagement valve 1-17 and can be placed in desired orientation by each in elution action. Also including a pair sleeve pipe according to actuating system 335 of the present invention, wherein in each joint port 18a and 19a becomes fluid-tight connect and provide low pressure or vacuum source to manifold 350. Preferably, manifold 250 is attachable to FASTlab^TM(being sold by GEHealthcare, Liege, BE) synthesizer, its sequencing operates valve and applies vacuum. Because FASTlab synthesizer has been designed for operating in the environment of hot cell, it is ideally suited as the actuating device of system 300. Actuating system 335 is by controlling system 326 according to the elution time table commander's action calculated.

Referring now to Fig. 8, it is shown that the eluting box 400 that multiple generator elution system uses together. In fig. 8, four aluminium oxide generator 110a-d for producing Tc-99m with decay Mo-99 illustrate and are connected with valve manifold 450. Box 400 includes the container 402 with smooth antetheca 404, and this antetheca 404 is demarcated by the perisporium 406 limiting container chamber 408. Box 400 supports elongate manifold 450 in the chamber 408 of adjacent bottom wall 406a. Manifold 450 is preferably based at the FASTlab sold by GEHealthcare, Liege, BE^TMThe linear plug manifold arranged used in box. Manifold 450 includes 25 3 logical/3 position plug valves 1 '-25 '. Valve 1 '-25 ' in each include contiguous manifold valve and be pointed to three open ports that corresponding Rule thereon is opened, this Rule port is between other relative ports. Each valve includes rotatable plug, and it makes any two fluid communication with each other in the port that these three associates be fluidly isolated the 3rd port simultaneously. It is still further contemplated that plug can include T-shaped inner passage wherein, to allow also to whole three ports be positioned to stride across valve fluid connection, but such embodiment will provide for dead space, it may require that other rinsing to prevent the flow losses occurring and being wherein trapped in dead space of pollution between continuous fluid flowing. Manifold 450 farther includes the first and second socket connectors 26 and 27 in its opposite end, each respectively limits vacuum ports 26a and 27a. Manifold 450 and valve 1 '-25 ' plug and catheter extension described below preferably formed with polymeric material, for instance PP, PE, polysulfones, Polyetherimide or polyether-ether-ketone. As figure 8 illustrates, although the actual number of valve is the adjustable needs meeting user, manifold preferably includes 25 3 logical/3 position plug valves. The valve not used can make their Rule connection be covered by Luer coupler simply, and their plug provides fluid communication to the flowing between adjacent valve.

Box 400 is the version of pre-assembled synthesis box, and it is designed to accommodate in installing with minimum client and connecting the Clinical lots synthesizing different radiopharmaceuticals. Box 400 preferably adopts kit form to provide, and this external member has to be connected to whole in the duct conduits of eluting nucleic and the adapter of support and filter of generator, bottle and eluant source or multiple source according to the present invention.Preferably, box 400 is supplied to user, has wherein made the conduit each connection to Rule of its valve so that only free end needs to coordinate with suitable member in tight. The box so provided can aseptically assemble and pack so that supply pharmaceutical operations if opened in suitable clean environment by maintaining suitable aseptic level.

Each in the connection at valve place described herein makes in the port, Rule limited by its luer connector. As figure 8 illustrates, valve 3 ' supports filtering outlet 351 in its junction, Rule. Valve 4 ' is connected to rinse streams body source 415 by slender conduit 452. Rinse streams body source 415 is between eluting runs or provides rinse fluid to be used for rinsing manifold 250 as required. Rinse streams body source 415 be preferably also connected with filtering outlet 433 communication assist eluant pass through conduit 452 towards valve 4 ' flow out. Namely, although it is contemplated by the invention that box 400 can provide as described in Fig. 5 and 8 for each single eluant source in eluting generator, in the embodiment in fig. 8, the present invention includes having as illustrated in fig. 1 each generator in the eluant source (providing in eluant bottle 130) of its own. There is provided each generator in the eluant source 130 with its own preferably to prevent the risk of the excess dilution of the eluate volume from public reservoir. It addition, by providing each generator in attached eluting source with its own, manifold valve 5 '-14 ' in multiple can be used for be connected to generator. The air outlet slit on the manifold vacuum for bleeding off too much or not using. The eluate passage 120 of generator 110a-d connects back to manifold 450 respectively through slender pipeline 460a-d. Conduit 460a-d is respectively at the corresponding eluate passage 120 of generator 110a-d to valve 15 '-18 ' between extend.

Valve 5 '-14 ' each covered by Luer coupler, Rule port of each valve of this fitting seal. Valve 5 '-14 ' can be used for scaling up box 400 to hold other generator (just in case user wishes so).

Valve 19 ' is connected to the input port of cation seperation column 415 by slender pipeline 462. Cation seperation column 415 is served and is always removed competing ions from the eluate of generator before concentration. Valve 20 ' is connected to the output port of cation seperation column 415. Valve 21 ' is connected to the input port of evaporating column 412 by slender conduit 465. Valve 22 ' is connected to the second eluant source 416 by slender conduit 464. Second eluant source 416 provides eluant from evaporating column 412 eluting daughter nuclide. Second eluant source 416 is also preferably fluidly coupled to filtering outlet 463 and assists the second eluant to be flowed out towards valve 22 ' by conduit 462. Valve 24 ' is connected to the output port of post 412 so that post 412 is preferably directly connected to valve 24 '.

The connection of waste material bottle and receiving flask be will now be described. Valve 23 ' is connected to the input port 472 of waste material bottle 419 by slender conduit 470. Valve 25 ' is connected to the input port 468 of receiving flask 418 by slender conduit 466. Valve 1 ' is connected to the output port 478 of receiving flask 418 by slender conduit 476. Valve 2 ' is connected to the output port 475 of waste material bottle 415 by slender conduit 474.

Example eluting be will now be described. Having calculated elution time table, its requirement is activity eluted from generator 110b and 110d. By applying vacuum (that is, enough low pressure) at port 26a, the first eluant will extract for generator 110b from the first source bottle 130.Valve 1 '-25 is set ' make the first eluant flow through generator 110b, by conduit 460b to valve 16 ' and by valve 19 '. Valve 19 ' guides eluate to flow through the conduit 462 input port to cation seperation column 415. Eluate will be extracted by valve 21 ' from post 415 and enter slender conduit 465 and enter the ingress port of evaporating column 412. Continuation is extracted and down to valve 23 ' and is entered waste material bottle 419 by valve 24 ' by post 412 by waste material. The volume of waste material bottle 419 will enough collect thus the liquid carried from post 412 whole.

Then the plug of changeover valve 16 ' isolates generator 110b, and the plug of changeover valve 18 ' makes the first eluant will extract from the bottle 130 being connected to generator 110d. Then eluate from generator 110d guides by conduit 460d to valve 18 ' and then arrives forward valve 19 '. Valve 19 ' guides eluate to flow through the conduit 462 input port to post 415. Eluate will be extracted by valve 21 ' from post 415 and enter slender conduit 465 and enter the ingress port of evaporating column 412. Continuation is extracted and down to valve 23 ' and is entered waste material bottle 419 by valve 24 ' by post 412 by waste material. From generator 110b and 110d daughter nuclide thus collect in evaporating column 412.

In order to from post 412 eluting daughter nuclide, valve 22 ' by lower for the suction being arranged in port 26a the second eluant guided from source 416 by conduit 464 and valve 22 ' and towards valve 21 '. Second eluant extracts and passes through the input port of post 412 and by post 412 by conduit 465. When leaving post 412 and entering valve 24 ', post 412 eluate will comprise daughter nuclide and be used for allotting entrance receiving flask 418. This eluate is directed to valve 25 ' and enters bottle 418 by conduit 466, applies from the valve 1 ' that is aspirated through of port 26a with conduit 476. Then bottle 418 can be removed or offer daughter nuclide of releasing is for being processed further by pharmacists. Subsequently from generator allot thus the identical receiving flask of bootable entrance or additionally with is combined from the eluate that do not use allotted before because the control system of the present invention it be used for from the calculating of generator 110a-d allocation, included any remaining activity to meet the requirement of demand data.

Box 400 is formed and is attached to actuating system, and it engages and arranges the orientation of plug of valve and provide low-pressure suction or vacuum for drawing fluid through manifold and entering bottle. Actuating system includes rotatable arm, its engagement valve 1 '-25 ' plug in each and in elution action, desired orientation can be placed in by each. Also including a pair sleeve pipe according to actuating system of the present invention, wherein in each joint port 26a and 27a becomes fluid-tight connect and provide low pressure or vacuum source to manifold 450. Preferably, manifold 450 is attachable to FASTlab^TM(being sold by GEHealthcare, Liege, BE) synthesizer, its sequencing operates valve and applies vacuum. Because FASTlab synthesizer has been designed for operating in the environment of hot cell, so it is ideally suited as the actuating device of box 400, come according to the elution time table handling calculated from controlling system its actuation instructions of reception.

For the box of the present invention and manifold system all embodiments (include Fig. 5, describe in detail in 7 and 8 those), box or manifold are preferably attachable to FASTlab device.All liq transmission is undertaken by the vacuum (or low pressure) applied. All connections to manifold box are envisioned for locks via standard Luer. It is preferably that the silicone terminated with barrier film allows to be penetrated by spicule 125a and 129a corresponding port on generator 110 for being connected to the conduit of generator. When eluant bottle 130 is attached to generator, standard can be used to connect. Generator works together with the present invention thus need not be revised.

Additionally for all embodiments, the external source of rinse fluid (such as water for injection (WFI)) can be connected to manifold for cleaning and rinsing purpose. When eluting gel generator, WFI source may be connected to each generator and also plays the effect of the first eluant. As particularly described for Fig. 8, it is contemplated by the invention that the first eluant can be from reservoir or pre-xylometer or is connected respectively to " the eluting bottle " of each generator. Prediction source is advisable to prevent the excess dilution of eluate volume and discharge the other manifold valve for being connected to generator. The air outlet slit on the manifold vacuum for bleeding off too much or not using.

It is still further contemplated that for some embodiments, depend on the eluting chemistry of requirement, the first source (as described for Fig. 5 and 7) being directly connected to the eluant of manifold can be used for eluting generator and evaporating column, thus avoiding the needs in the second source to the eluant being connected to manifold. Such as, if the system of Fig. 7 300 adopts aluminium oxide generator and aluminium oxide evaporating column, it is contemplated by the invention that the first source of eluant can provide saline solution, it is for eluting generator with for eluting evaporating column.

Cation seperation column for removing the competing ions such as such as chloride from eluate. In certain embodiments, pertechnetate ion flows through cation seperation column and the acidified alumina post of be here captured forward (concentration) to it. Liquid is allowed to flow through post and enter waste collection reservoirs for processing in the future. Acidified alumina post (as stated) be used for catching and concentrate pertechnetate (^99mTc). Although pertechnetate catches on alumina column, but liquid (substantially water) is removed by vacuum from the bottom of post and collects waste material container. Once concentration step completes, alumina column preferably substantially adopts pertechnetate with current fission generator exact same way small size saline solution eluting as sodium pertechnetate [Na^99mTcO_4-] remove, and collect in product collection bottle.

Determine with reference to Fig. 9, user demand data of the present invention and supply data and perform parent-daughter generator group maximal efficiency in radiopharmaceutical operates and utilize. These supply data allow (daughter nuclide) Useful active amount automatization at any given time to calculate. Generator is sold and is had the activity of known quantity. These supply data can input from generator bar code or artificial data and obtain. This demand data is to meet the live vol of customer order in special time requirement. Data can via electric transmission from such as SAP or Slimline(or equivalent) etc. ERP software system, or by being manually entered. Typically, in radiopharmaceutical environment, customer order is divided into the conveying being ranked some time of one day to carry out.

The present invention compare demand Active pharmaceutical with at any given time can activity. It addition, system proposes to represent the best fit scheme being used for the optimum efficiency from given generator eluting by attempting configuration generator eluting plan.Once this best fit computation schemes goes out, operator has some options: a) perform the eluting plan determined by system, b) eluting plan-allow system-computed is manually reconfigured and to operator's display effect, or c) by inputting some demand and require and/or supply data and look back the elution time table of the calculating determined under the constraint of input by system and simulate ' what-if scene '.

When confirming that the eluting plan calculated is acceptable from operator, the present invention sends data to the generator that actuating system to select according to elution time table eluting. Such as Tc-99m is concentrated on alumina column by the eluate from the generator selected all through box. Once all generator eluting complete, alumina column is eluting in wanting the eluant (typically 5-6mL) of such as saline solution of cube. Once this operation completes, the change of any requirement of control system updates activity data, recalculates growth and updates elution time table.

Generally, ERP system is integrated computer based application, and it is used for managing inside and outside resource, including physical assets, financial resources, material and human resources. Its purpose is easy for information flowing between all business functions in the scope of tissue, and manages the connection of external stakeholders. Being based upon on centralized data base and the public calculating platform of general, all business operations are combined into unified and enterprise-wide system environments by ERP system. ERP system may reside within centralized server, or cross-module massing hardware and software cell distribution, and it provides " service " and communicates on a local area network. Distributed Design allows the business assembling the module from different suppliers without the multiple copy placing complicated and expensive computer system in the region of the whole abilities by not using them.

The method of the present invention is thus including input step 610, and wherein each supply data in generator are input to the reception unit of elution system. Then the method includes inputting from the how much active second step 620 with demand data when to reception unit of multiple generator requirements. This heel calculates and selects step 630, wherein determines each suitable time of eluent table in multiple generator according to the supply data of input and the demand data of input. This calculating and select step 630 preferably compare active current demand, activity future demand and at present and demand point subsequently or elution time from generator can activity, and select by which generator of eluting with when to minimize the waste of the daughter nuclide produced in meeting demand data by generator. But, there is elution step 670, wherein daughter nuclide from select generator eluting.

Step 610 farther includes to input the calibration data (typically the activity of each generator and date) 612 of each generator, input generator can time and date 614 and the step of time and date that deviates from the reference time of input the first eluting. Step 612,614,616 manually can carrying out to receiving unit by being manually entered each information in these steps, such information is normally provided to each generator. Alternatively, step 612, the 614 and 616 such information of bar code scanning that can pass through to be subordinated to each generator carry out electronically or automatically. Equally, step 620 can manually or electrically carry out, and wherein demand data is generally supplied by ERP system.For manually carrying out step 620, operator is by acquirement demand data information and inputs into reception unit. Operator preferably, when being manually entered demand data, receives unit or control system will be compiled into demand data collection information, although also can carry out this compiling before input amounts to demand data. Alternatively, ERP system can communicate so that individual order is automatically entered into the elution time table of system and calculating electronically with receiving unit.

It is still further contemplated that step 610 can include the step 618 of input given data constant. Step 618 can provide for considering such data constant in act 630. These data constants preferably include the time expiration of the mark of eluting available in parent nuclide half-life and decay equation, daughter nuclide half-life and decay equation, eluting output efficiency, parent nuclide decay, the equilibrium equation of parent-daughter activity and generator.

The fixed interval such as step 630 includes preferably adopting such as 30 minutes calculate the step of Useful active of 632 and display 634 each generators. Preferably, calculation procedure 632 adopts equation (1) and step display 634 to show the activity in each generator with the interval calculated. Additionally, step 630 can include the generalized reduced gradient Algorithm Analysis carrying out the activity level of demand data and multiple generator to determine that suitable time of eluent table is for minimizing waste. Alternatively, step 630 imagination runs the simulation of the various elution time tables from multiple generators, and selects the elution time table causing the daughter nuclide of minimum to be wasted when meeting demand data. It addition, the method preferably includes and supplies the step 638 showing demand data on the interval that data are identical. Step 630 preferably farther includes to calculate the step 638 of best fit elution curve or timetable, for select in available generator which by preset time eluting to adopt possible most efficient way to meet demand data, thus maximizing the useful life longevity of each generator and minimizing waste. Then the method can include providing elution time table to the step 640 of operator.

Preferably, the display of elution time table provides and method upper at graphic user interface (GUI) to include giving the step 642 that operator is ranked option that different generators makes the optimization elution time table of calculating invalid for the eluting in preset time by replacement. If operator's refusal makes system in effective, then method proceeds to send eluting instruction to the step 660 of actuating system. If operator selects to make the eluting instruction ignore from step 638, method farther includes operator and is manually entered the step 644 of the amendment to elution time table. Step 644 allows operator to choose when specific for eluting generator. Then method includes recalculating elution time table 646 and shows the step 648 of the time that is ranked of active availability that each generator updates in time and each eluting from generator. Considering any other operator's constraint, step 646 preferably adopts the algorithm identical with step 630 in determining suitable time of eluent table. Then method includes prompting operator and accepts the step 650 of the elution time table updated. If operator accepts the elution time table updated, elution time table will be set and control system and will provide for suitable instruction and be used for generator eluting, step 660 to actuating system.If operator does not accept the elution time table updated, method by repetitions step 644,646 and 648 accept elution time table until operator. Once the elution time table updated is satisfied for operator, method proceeds to step 660.

After step 660, actuating system will carry out step 670, and according to elution time table eluting generator. Step 642,644,646,648 and 650 provide ' operator is in the loop ' option to monitor and manage the eluting from generator, and allow operator to make the timetable of calculating invalid. Under any circumstance, the present invention is operable to intervene without operator and such that it is able to the eluting that automatically carries out being ranked inputs a timetable without operator, thus make operator free and turn to other pharmacy responsibilities. However, it is believed that certain point in the circulating cycle provides operator to be advisable to accept elution time table.

After elution step 670, method can include validating that the step 672 of the generator that eluting selects. If it addition, method preferably includes recalculating Active Growth 674, the activity data revised in step 632 and needing, repeating step 638 and below step recalculate best fit elution time table for meeting demand data.

The present invention further provides the computer program for managing the eluting from multiple generator elution system according to the present invention. The present invention further provides multiple generator elution system, it includes the computer hardware of the computer program for performing the present invention. This computer program includes computer usable medium, and it has the computer usable program code of the method for carrying out the present invention. This computer program code includes computer usable medium, and it has the computer usable program code of management multiple generator elution system. The supply data of the input of many parent-daughter generators are received from generator and to the active demand data from generator including the computer program of computer usable program code. Computer program farther includes: computer usable program code, and it calculates the elution time table of generator based on the Useful active in generator and demand data; And computer program code, it guides the actuating system of the elution system generator eluting to select from generator according to this elution time table.

Computer program preferably farther includes for showing the Useful active in supply data, demand data, generator and the computer program code of at least one in elution time table. It addition, this computer program code calculating elution time table also includes the generalized reduced gradient Algorithm Analysis of the activity level for carrying out demand data and multiple generator determines the computer program code of the optimization elution time table for minimizing waste. Alternatively, the computer program code for calculating elution time table also includes the simulation for running the various elution time tables from multiple generators and selects the computer program code of the elution time table causing when meeting demand data the daughter nuclide of minimum to be wasted. Computer program preferably also includes for allowing operator by inputting the new computer program code being tied to computer program and make the elution time table of calculating invalid, and calculates the computer program code of new elution time table for the constraint new based on these. Additionally, computer program preferably includes for storing supply data, demand data and elution time table for the computer program code of retrieval in the future and can being the purpose service that record keeps or record support keeps.

Figure 10 describes the screenshotss of the graphic user interface (GUI) of the present invention for providing supply data message to the multiple generator elution system of the present invention.Figure 10 illustrates supply data entry screen 700. Screen 700 provides MicrosoftExcelScreen, it is shown in row A, row 6-11 the supply data of six generators listed. Row B, row 6-11 list the reference time of each generator. Row C, row 6-11 list the first eluting deviation (in hours) each in the generator listed. The entry lacked will be regarded as zero offset. Row D, row 6-11 list each generator initial activity in the reference time. Row E, row 6-11 list when each generator may be used in. As the error checking to Data Entry, the reference time in row A must be before at least ten two hours of the time that may be used in row E. Row F, row 6-11 will illustrate any error message of each generator. Row E, row 2-3 provide the net efficiency of generator, or eluting output efficiency, and typically about 0.83.

Figure 11 describes the screenshotss of the GUI of the present invention for the elution time table providing to Figure 10 six generators to calculate. Figure 10 illustrates eluting management window 800, and it provides the supply data of multiple generator elution system, demand data and elution time table. This is based on demand balance efficiency and the active worksheet needed in the future or best fit result. Although the feature of the relevant information in Figure 11 display line 46 to 69, it represents from 9:30 in morning July 12 in the 10 o'clock to 2010 afternoon of on July 11st, 2010, and the information of window 800 continues during the generator life-span, two weeks and can roll typically. Row A, row 46 to 69 provide interval time, and calculating and the allocation of this interval time occur during the period illustrated. Interval is provided with 30 minutes intervals. Row D, row 46 to 69 list the time that data distribution must occur according to demand. The time listed makes nucleic with desired state to the process time of the state required by user after considering eluting. Thus, for instance, row D illustrate eluting by the 12:00 in the morning of Monday on July 12nd, 2010, the morning 2:00, the morning 4:00 and the morning 7:00 run. It is rolled to the unsighted demand being about to illustrate the time after a while and other information further downward. Row E provides the balance from untapped any previous eluting to remain, and advance illustrates decay in time. The generator eluting that row F, P, Z, AJ, AT and BD mark for being expert at 1 respectively, list in row G, Q, AA, AK, AU and BE is ranked when. In activity from numeral ' 1 ' being input to when corresponding generator eluting row F, P, Z, AJ, AT and BD. As can be seen, for the generator of each eluting, the next line after eluting illustrates the activity of much less, and after its instruction eluting, Active Growth occurs.

As, shown in row D, row 50, there is the demand for 14,350mCi activity at midnight (row 50). Control system-computed in order to the best meet in the known demand in row D whole, eluting is met this demand by generator 1 and generator 5, it is provided that 27mCi does not use surplus, and it can include eluting in the future in. Similarly, eluting (row 54) at 2:00 in the morning, in order to meet for 15, the demand of 931mCi activity, 2405.5mCi activity will from generator 2 eluting, the activity of 2405.5mCi will from generator 3 eluting, and 11,120.5mCi activity will from generator 4 eluting, it is provided that 22mCi does not use surplus. Also being included within this eluting from the remaining activity of eluting before, therefore current eluting can not be amounted to, by themselves, the demand obtaining listing in some instances.

Operator can by deleting ' 1 ' from eluting row and selecting another generator to make from its eluting the elution time table of offer invalid. Control system by the entry refilled in window 800 to illustrate new elution time table and activity available in each preset time each generator, any surplus in the demand and remaining activity of each elution time. The simulation feature of the present invention allows such as when generation is impacted in supply, and the present invention is for assessing the impact of " what-if " scene and particularly useful finally for the dosage that given supply situation conveying is maximum. Under any circumstance, when elution time is satisfied with by operator, it can be stayed alone automatically to run as shown. Utilizing the eluting that automatically carries out, operator turns to other responsibilities by what be not affected by constraint. It addition, software provides the record of the eluting carried out, simplify record and keep purpose. Although additionally, six generators followed the tracks of by supply data screen 700 and eluting management window 800, but the present invention is adjustable, wherein it can be monitored and the as many generator including in multiple generator elution system.

The present invention radiotropism pharmacy can provide cost savings. The Largest Single Item cost of radiopharmaceutical is Tc-99m/Mo99 generator, and it is used for constituting " cold external member " (diagnostic reagent). Illustrate that average pharmacy generator efficiency is 65-68% with the action of experienced radiopharmacist test. After new tool realizes, average efficiency is stably increased to 98-100%. Typically, average pharmacy can consume four 18Ci generators for one week. Each generator has the useful preservation life-span of two weeks. Thus on basis weekly, pharmacy will need the decay by them of eight generators of management and uses circulation. Currently, using weekly four 18Ci unit with $ 7000, each is the cost of annual $ 1.456MM. If its efficiency is brought up to 100% from 65% by identical pharmacy the application of the invention, annual cost reduces about $ 0.5MM.

Although there has been shown and described that the particular embodiment of the present invention, can make a change for those skilled in that art and revise and will be apparent from without departing from the teachings of the present invention. In description above and accompanying drawing set forth purport only by illustrate provide and without limitation. The actual range of the present invention be intended to when based on prior art objective check following claim all sidedly time limit in these claim.

Claims (22)

1., from a method for multiple parent-daughter generator eluting daughter nuclides, comprise the following steps:

Input supply data are to elution system, and described supply data include the information allowing to calculate the Useful active in described generator;

Input demand data is to described elution system, and described demand data at least includes the timetable of the amount of the exit dose of daughter nuclide and the described daughter nuclide of generation to produce;

Calculate based on described demand data and select each suitable time of eluent table in the plurality of generator, described calculating and select step by current demand, in the future demand with at present and demand point subsequently from the plurality of generator can activity compare, in order to minimize the waste of the daughter isotope produced by the plurality of generator when meeting described demand data;

Daughter nuclide according to the generator eluting that described suitable time of eluent table selects from the plurality of generator;

The described daughter nuclide of each collection from the generator selected described in the plurality of generator in evaporating column;

Described daughter nuclide is eluted into collecting container from described evaporating column.

2. farther include to carry out the generalized reduced gradient Algorithm Analysis of the activity level of described demand data and the plurality of generator from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said calculating and selection step as claimed in claim 1.

3. as claimed in claim 1 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said calculating and selection step farther include to run the simulation of the various elution time tables from the plurality of generator, and select the elution time table causing the described daughter nuclide of minimum to be wasted when meeting described demand data.

4. as claimed in claim 1 from the method for multiple parent-daughter generator eluting daughter nuclides, the described step wherein inputting demand data farther includes to input described demand data to receiving unit, and described reception unit provides described demand data to controlling system.

5. as claimed in claim 4 from the method for multiple parent-daughter generator eluting daughter nuclides, the described step wherein inputting demand data farther includes to be manually entered described demand data to the step receiving unit, and described reception unit provides described demand data to described control system.

6. as claimed in claim 4 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein input the step that the described step of demand data farther includes to automatically enter described demand data electronically to reception unit.

7. as claimed in claim 6 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein automatically enter described demand data electronically and farther include to receive from network order processing website the step of described demand data to the described step receiving unit.

8. being undertaken from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said calculating and selection step by controlling system as claimed in claim 4, described control system receives described demand data from described reception unit.

9. as claimed in claim 1 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said input supply data step farther includes the step of the time and date of the first eluting deviation of the date and time inputting the calibration data of each generator, each generator may be used in, each generator.

10. the time expiration of parent nuclide half-life, parent nuclide decay equation, daughter nuclide half-life, daughter nuclide decay equation, eluting output efficiency, decay from the parent nuclide mark of eluting, equilibrium equation and each generator that can use is considered as claimed in claim 1 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said calculating and selection step.

11. as claimed in claim 1 from the method for multiple parent-daughter generator eluting daughter nuclides, further include steps of

Display as the Time Calculation for timetable the plurality of generator each in can use activity;

Locate to show described demand data in the table in the time of timetable; And

Show the elution time table curve from described calculating and the selection selecting step.

12. as claimed in claim 11 from the method for multiple parent-daughter generator eluting daughter nuclides, further include steps of

The elution time table curve manually making described selection is invalid;

Calculate result from described permission step surmount elution time table curve;

Show and described in described permission step, surmount elution time table curve; And

Allow operator confirm described in surmount elution time table curve and surmount described in manually making elution time table curve invalid in one of.

13. as claimed in claim 12 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said artificial invalidation step farther includes to select the step of those generators by the time eluting at elution time table in the plurality of generator.

14. as claimed in claim 1 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein the described step of input supply data calculates the growth activity level of the generator selected described in the plurality of generator after further including at described elution step.

Undertaken by controlling system from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said calculating and selection step and described elution step 15. as claimed in claim 1.

16. as claimed in claim 15 from the method for multiple parent-daughter generator eluting daughter nuclides, wherein said control system carries out each described elution step according to selected suitable time of eluent table without other operator's input.

17. for the device managing the eluting from multiple generator elution system, including:

For receiving the parts of the supply data of the input of many parent-daughter generators;

For receiving the parts of the demand data of activity from described generator;

For calculating the parts of the elution time table of described generator based on the Useful active in described generator and described demand data; And

The parts of the generator for selecting from described generator with eluting according to the actuating system of the described elution time table described elution system of guiding.

18. device as claimed in claim 17, farther include for showing the Useful active in described supply data, demand data, described generator and the parts of at least one in elution time table.

19. device as claimed in claim 17, wherein calculate the described parts of elution time table and farther include the generalized reduced gradient Algorithm Analysis of the activity level for carrying out described demand data and the plurality of generator and determine the assembly of the suitable time of eluent table for minimizing waste.

20. device as claimed in claim 17, wherein the described parts for calculating elution time table farther include: for running the simulation of the various elution time tables from the plurality of generator and selecting the assembly of the described elution time table causing when meeting described demand data the daughter nuclide of minimum to be wasted.

21. device as claimed in claim 17, farther include for allowing operator by inputting the new assembly being tied to described device and make the elution time table of described calculating invalid, and for calculating the assembly of new elution time table based on described new constraint.

22. device as claimed in claim 17, farther include for storing described supply data, demand data and the elution time table parts for retrieval in the future.