CN102971800A - Multiple generator elution system - Google Patents

Abstract

A multiple generator elution system for selectively eluting from a plurality of parent-daughter generators (110a-d) according to an elution schedule it calculates taking into account supply data, demand data, and available activity in each of the generators.

Description

The multigenerator elution system

Technical field

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

Background technology

The Mo-99 supply that fission produces is in nondeterministic statement.About 60-70% of world's supply of the Mo-99 that produces of two reactors (Canadian NRU reactor and Pei Teng (Petten) HFR reactor) representative fission only.When any off-line in these reactors (no matter being for the maintenance that is ranked or for the non-maintenance that is ranked), in fact the result reduces to nuclear medicine procedure only requisite case., currently only plan one and replace reactor just near the end in their relevant work life-spans for the manufacture of all reactors of fission Mo-99, pendant Teng who is called Pallas replaces.Concerned in addition is the diffusion of the highly enricked uranium (HEU) (target that is used for fission Mo-99) that falls into the hand of terrorist or rogue government.HEU is for the manufacture of nuclear weapon.

Alternatively, use the Mo-99 that obtains from the neutron activation (n, γ) of natural molybdenum based on the generator of gel, this neutron activation can be carried out in comprising any nuclear reactor of power reactor.Unfortunately, when with from U-235(no matter be HEU or low-enrichment uranium (LEU)) the Mo-99 that produces of fission when comparing, from n, the Mo-99 that the γ method produces is tending towards having low specific activity (specific activity).Low specific activity means that Mo-99 must be placed on and absorbs all sluggish molybdenums on the very large alumina column, or becomes insoluble gel-in-matrix (matrix), but the cumulative volume of its minimizing wash-out post (for example molybdic acid zirconium or molybdic acid titanium).Subsequently, require large elution volume to come wash-out Tc-99m daughter nuclide (daughter nuclide) post, if particularly use alumina column.Prior art fails to solve the whole issue that low specific activity and/or low activity generator run into.

Nucl.Med.Comm., 25 609-614 (2004) discuss from molybdic acid zirconium gel generator obtain the high radioactivity concentration of Tc-99m needs (for " cold external member (cold-kit) " consist of and larger radiation pharmacy because economic cause usually requires higher concentration).

United States Patent (USP) 5,729,821 open methods for the concentrated Tc-99m of the Mo-99 adsorbent from the post of alumina base.The a plurality of posts of system requirements are realized the concentrated of eluate (eluate).Because Tc-99m by with salt solusion in chlorion ion-exchange and wash-out leaves principal post, so must use a plurality of posts.Kation (sodium) is then removed by secondary post (being the halogenation money base in this case), and pertechnetate (pertechnetate) concentrates for forming Sodium Pertechnetate with the salt solusion wash-out subsequently in three anion columns.The method requires that Mo-99(for example from parent nuclide (parent nuclide) with Tc-99m with acid salt or weak acid, alumina column) separately and wash-out, and with cation seperation column kation is removed from wash-out, so that high technetium acid ion (pertechnetate ion) can be concentrated on the anion column.

The open method of extracting Tc-99m from the solution that contains Mo-99 of application of radiation and isotope (Applied Radiation and Isotopes) 66 (2008) 1814-1817.This is complicated operation, and its requirement with an organic solvent (tetrabutyl ammonium bromide (tetrabutylammonium bromide) solution in methylene chloride (methylene chloride)) comes extraction and concentration Tc-99m.

The open conduct of application of radiation and isotope 66 (2008) 1295-1299 is the method for the version of method above, and wherein low specific activity alumina base generator removes Tc-99m with the salt solusion wash-out.Eluate is concentrated on the SAX Dowex post.Tc-99m is by removing for being collected in the bottle with the tetrabutyl ammonium bromide eluant solution with methylene chloride.Organic solvent is used for using with cold external member by being vacuum-drawn against drying and removing and restoring with salt solusion.Because prepare the time that concentrated Tc-99m requires, the method is unpractiaca.

United States Patent (USP) 6,157, the 036 open method that is used for low specific activity ion-exchange type generator (being aluminium oxide).System uses on method and U.S. Patent number 5,729,821 similar a plurality of posts.It is intrinsic safer for the transfer that relates to radioactive material that the method replaces safer negative pressure to come mobile fluid-negative pressure (vacuum) with malleation.

Therefore the system that manages the growth of daughter nuclide for the efficient purpose need to be arranged.Also need to have elution system in this area, its minimum waste and maximization are by the use of the daughter nuclide of a series of generators generations.The elution system that the spread risk that can reduce HEU further need to be arranged.Need that also the manifold external member is arranged (manifold kit), it can be used for and will be directed to receiving flask from the eluate of a series of generators by the operation of robotization actuating system.

Summary of the invention

In view of the needs of this area, the invention provides the multigenerator elution system, it comprises a plurality of parents-daughter nucleus generator and control system, this control system be used for to be followed the tracks of each the growth of activity of these parents-daughter nucleus generator.

Control system receives the demand data of the active requirement that produces of indication, and is configured to the generator selected from generator with the first eluate wash-out, in order to the desired amount of daughter nuclide is provided.Receiving element receives demand data, the timetable that it comprises at least the amount of the daughter nuclide that will produce and produces the amount of this daughter nuclide.This receiving element can operate with control system, and daughter nuclide satisfies the demand that is represented by this demand data from the wash-out of a plurality of generators so that control system will be ranked.This receiving element also will receive supply data.

The present invention also provides evaporating column to be used for collecting the generator daughter nuclide from the generator that a plurality of generators are selected.This evaporating column comprises suitable post medium.For example, when the daughter nucleic was Tc-99m, evaporating column preferably was that daughter nuclide is from the anion column of its wash-out.Provide equally for the collection container that receives daughter nuclide from described evaporating column.

In addition, the invention provides control system multigenerator elution system, its follow the tracks of in parent-daughter nucleus generator each the growth of activity and the demand that from the generator wash-out of being ranked satisfies the input of daughter nuclide.

The present invention also can provide the second eluant, eluent source to come the wash-out post.Depend on application, this second eluant, eluent can be different from the first eluant, eluent or both are identical.In addition, coming with identical eluant, eluent among the embodiment of wash-out generator and evaporating column, eluant, eluent can extract from single source.Alternatively, the source of the first eluant, eluent can offer respectively each generator, rather than from common source.The present invention also provides when being provided for the wash-out generator such as high purity waters such as waters for injection from public reservoir, and this water also is used in the parts of rinsing elution system between the wash-out operation.The purpose that can provide high-purity water source only to be used for the parts of rinsing multigenerator elution system also is provided in the present invention.

In addition, the present invention also is provided for operating the method for multigenerator elution system, it coordinates the input demand data of the daughter nuclide that produced by generator, follows the tracks of in time available activity in each of generator, and from the generator wash-out of being ranked satisfies this input demand of daughter nuclide.

In addition, the invention provides the external member of manifold system, it can will be directed to separating column from the wash-out in a plurality of parents-daughter generator by the control system operation.

The present invention solves those technician's of the generator in management and the pharmacy of operation nuclear problem.For the purpose of illustration and non-limiting purpose is used the Tc-99m/Mo-99 generator, the present invention in conjunction with and concentrated daughter nuclide technetium [Tc-99m] pertechnetate wash-out from the multigenerator unit, and prolong the useful life longevity of decay or low activity generator.The present invention is together with automatically managing isotope " growth " with maximal efficiency and cost savings from the demand data of ERP system or artificial input.The present invention also allows operating personnel to simulate " what-if " scene, such as when simulation short supply and the unexpected increase in demand etc.In addition, after the present invention can be contained in the radiation barrier thing, this screen safe storage generator, and all process radioactive parts.The present invention allows gamma gel base Mo-99 generator to compare in operation more competitive with the fission base generator, thereby be convenient to the practicable alternatives by radiogenic Mo-99 of highly enricked uranium (HEU), thereby and reduce the diffusion of nuclear bomb level material.In addition, the present invention provides the exchange of prescription composition data to electronic health record.

The Mo-99 isotope that in the Tc-99m/Mo-99 generator, uses typically represent generator total cost 75% or more.Generator and isotope are bought maximum typically single expense item.Mo-99 decays into Tc-99m with known index percent, and Tc-99m is also with known index percent decay.Typical generator comprises the activity of known quantity when delivery.When this generator wash-out, remove Tc-99m and stay Mo-99 and continue to decay into Tc-99m.The calculating of accurately determining at any given time the amount requirement of available Tc-99m on the generator is very complicated, and is not easy to carry out.The invention provides control system, it comprises for the software of carrying out easily and fast these calculating.Utilize this software to allow control system to select the efficient combination of generator for any given demand together with the multigenerator elution system.In addition, history or real-time requirement can obtain by the artificial input of operator or by the data link from enterprise resource planning.

Molybdic acid titanium " gel " base generator uses low-down specific activity Mo-99, and it causes the less wash-out that concentrates and have generally lower than industrial standard fission Mo-99 base generator gross activity content.This multigenerator elution system of the present invention is got rid of these problems and is allowed the gel base generator more competitive in operation than industrial standard fission base generator.

Description of drawings

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 in the Mo-99/Tc-99m generator behind the continuous wash-out of Tc-99m isotope ion.

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

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

Fig. 6 describes the multigenerator 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 as the part of multigenerator elution system of the present invention.

Fig. 9 is the process flow diagram of describing method of the present invention.

Figure 10 describes for the screenshotss that the graphic user interface of the present invention (GUI) of information provision is provided to multigenerator elution system of the present invention.

Figure 11 describes the screenshotss for the GUI of the wash-out management system of multigenerator elution system.

Embodiment

The concentrated eluate from the large volume wash-out of the present invention is used for requiring more " cold external member " recovery of high radioactivity concentration.In one embodiment, the invention provides for the system that concentrates Tc-99m.The present invention can concentrate eluate and realize workflow efficiency in larger radiopharmaceutical, the QC for eluate tests especially, and gets rid of the respectively time of a plurality of generators consumption of wash-out.In addition, the present invention's generator (thereby it is because low yield and the lower radioactive concentration of eluate are tending towards not using) of allowing to close on expiration uses more fully expiration and realizes cost savings.The present invention comprises software and mates better demand and supply, thereby realizes cost savings and minimum waste and loss.The present invention avoids the needs to an organic solvent, thereby gets rid of waste and the use of harmful organic solvent.

The invention provides the multigenerator elution system, it uses a plurality of parents-daughter generator, follows the tracks of the growth relationship of the parent-daughter isotope of these generators in each, and the output of these generators of concentrated wash-out.With in these concepts whole three combine solve about low specific activity generator use and service efficiency in intrinsic problem.

The multigenerator elution system preferably is enclosed in the radiation shield shell, such as plumbous wall hot cell etc.Be used for management from the wash-out of single generator although the present invention will work, manage in a preferred embodiment a plurality of generators.One embodiment of the present of invention are utilized many Mo-99 titaniums/Tc-99m titanium [Mo-99] molybdate gel generator, and it utilizes the Mo-99 that obtains from the neutron activation of natural molybdenum (n, γ Mo-99).Although make with particular reference to managing from the wash-out of Mo-99/Tc-99m parent-daughter generator, the present invention's imagination also can adopt the generator of other types to come wash-out and other daughter isotopes or daughter nuclide.

Thereby in one embodiment of the invention, the shell of lead shield comprises one or more Mo99/Tc99m generators.These generators link together via the fluid path system, and it can be eluted on evaporating column or a plurality of post any combination of generator.In the situation of Tc-99m, this evaporating column is cathode column.Concentrated Tc99m subsequently wash-out leaves this evaporating column to be ready to entering receiving flask for the radioactive concentration of the requirement in radiopharmaceutical.Control system is selected the most efficient combination of generator in the future based on demand, available supply and demand.

Current and the demand in the future of the available supply of activity and activity can be respectively from generator self and from radiopharmaceutical Enterprise Resources Plan (ERP) system manually input or electronically transmission enter receiving element and metering-in control system.For example, can read electronically or scan from the label (such as bar code etc.) on the generator from the data of generator self transmission.Can comprise the calibration data of generator about such data (also being called ' supply data ') of generator, provide the date and active both.In addition, the imagination supply data comprises the time and date that time and date that generator can be used for using and the first wash-out depart from.Similarly, comprise the active of requirement and can be manually or input control system electronically from the demand data of time of the such activity of system requirements.The present invention imagines the configuration data receiving element and is used for the artificial of demand data and/or electronics input.

Use supply data, control system can preferably be calculated activity available in each generator so that interval (for example every 30 minutes) to be set, and displays it to the operator.Demand data preferably similarly shows on the time interval identical with supply data.Control system comprises that computing machine calculates best-fit elution curve or timetable, be used for to select and to come with the possible efficient way data that satisfy the demands at wash-out preset time with which of generator, thereby maximize useful life longevity and the minimum waste of each generator.Preferably sequencing of control system is carried out the broad sense reduction gradient algorithm of the activity level of demand data and a plurality of generators and is analyzed to determine that the suitable time of eluent table is used for minimum waste.Alternatively, the present invention imagines the control system sequencing and moves from the simulation of the various elution time tables of a plurality of generators, and selection causes the elution time table of the daughter nuclide waste of minimum when satisfying the demands data.This elution time table also will offer the operator.

Preferably, being presented on the GUI of elution time table provides, and it gives the operator by replacing being ranked different generators for the invalid option of optimization elution time table that makes calculating at the wash-out of preset time.When the operator determines to revise the elution time table, control system will recomputate the elution time table and show active availability that each generator upgrades in time and being ranked the time of each wash-out from generator.If the elution time table that upgrades is satisfied for the operator, will be in accordance with the wash-out instruction for the generator of selecting according to the timetable wash-out.Like this, the invention provides ' operator is in loop ' option and monitor and manage wash-out from generator, and allow the operator to make the timetable of calculating invalid.Alternatively, need not the operator thereby the present invention can operate and intervene and can automatically be ranked wash-out and do not have the operator to input, make thus the operator free to turn to other pharmacy responsibilities.

The wash-out of the generator that the wash-out instruction will be selected for Electronic Control.When the wash-out generator, control system will be upgraded growth calculating and upgrade elution time table (if necessary).The present invention imagines the operator or system will confirm the in fact eluted step of the generator of selecting.

The known constant such as mark such as wash-out available in parent nuclide half life period and decay equation, daughter nuclide half life period and decay equation, wash-out output efficiency and the parent nuclide decay will be preferably considered in the calculating of using in filling the elution time table.In addition, control system will be considered the balance equation of parent-daughter and the time expiration of generator.Most of generators had for 2 life-spans in week (this be pharmacy expiration require), if but the parent isotope (for example, Sr-90/Y-90) then it can be much longer have the long half-lift.

The invention provides many technology and economic advantage on both.Thereby the present invention can be as carrying out for the concentrator of each wash-out operation from the activity of the generator wash-out of selection.This not only allows the efficient utilization of generator, and the generator that it also allows to close on expiration still can the combination with one another utilization, and this is because their activity is concentrated in together.Automation mechanized operation can reduce the pharmacy office worker and be exposed to dosage.The same efficiency that realizes.For example, if four generator difference wash-outs then require four distinct quality controls tests.The present invention allows concentrated wash-out is only carried out single quality control test by concentrated individual wash-out, allows more activity to be retained in the receiving flask for clinical.

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

System preferably comprises the shielding area of accommodating two or more gel generators.These generators connect to come separately valve manifold, and it can select the generator of selecting at the reasonable time wash-out to satisfy the demand of being planned by control system.Tc-99m by make eluant, eluent by one or more generators of selecting wash-out.Tc-99m collects at the aluminium oxide evaporating column.When finishing from the collection of generator, control system enters the receiving flask of industrial standard shielding with this evaporating column of eluant, eluent wash-out.This eluant, eluent can extract the wash-out generator from the reservoir of current usefulness or from individual bottle of saline solution.

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

Put down in writing the whole bag of tricks of concentrated Tc-99m wash-out.The calculating that is used for the growth relationship of definite parent daughter isotope is well-known, but owing to complicacy is seldom used.N, the use of γ Mo-99 in gel generator system and other generator systems also is known.The present invention combines and enters individual system whole three in these concepts, and it manages the supply data of a plurality of generators, available activity and demand data, and overcome about low specific activity generator use and service efficiency in intrinsic problem.

The present invention will work together with molybdic acid zirconium or molybdic acid titanium gel generator system.Utilize and revise, the present invention's (as describing in detail) will work together with the alumina base system equally.To work together with the alumina base system, therefore will require other post and fluid path.

Proved the concept of molybdic acid titanium gel Generator Design.This gel produces with irradiation behind the natural molybdenum of irradiation.The method of setting up comprises the preformed gel of irradiation or molybdenum trioxide.The irradiation metal carrying is for output, security and treatment effeciency advantage.

Referring now to Fig. 1, prior art and parent that include multigenerator elution system of the present invention in-daughter generator 110 comprises long-life parent-nucleic, and it decays into more short-life daughter nuclide.Because parent and daughter nuclide are not isotopes, the chemical isolation daughter nuclide is possible.The guiding eluant, eluent is by comprising the post of parent and daughter nuclide, but only takes away daughter nuclide as the eluate from this post.Behind wash-out, parent nuclide (being retained in the generator) will decay to provide the fresh supply of daughter nuclide.Thereby generator can provide the fresh supply of daughter nuclide as required until exhaust the parent activity.

Generator 110 comprises uses the generation body 112 that forms such as radiation shielding materials such as lead.Body 112 occurs limit the post chamber 114 that comprises the post 116 that keeps parent nuclide.Body 112 occurs limit elongated eluant, eluent passage 118 and elongated eluate passage 120, its respectively fluid connection extension between post chamber 114 and eluant, eluent chamber 122 and collecting chamber 124.Post 116 comprises medium 126, parent nuclide and its combination, but daughter nuclide wherein can be from its wash-out.Eluant bottle 130 and collecting chamber 124 supports receiving flask 132 are wherein supported in eluant, eluent chamber 122.Eluant, eluent conduit 134 fluid between eluant bottle 130 and post 116 is communicated with extension in order to enter post 116 from bottle 130 interior conveying eluant, eluents.At every end, eluant, eluent conduit 134 stops at elongated spicule 125a and 125b for the barrier film that pierces through bottle 130 and post 116 respectively.Eluate conduit 136 extends to receiving flask 132 in order to eluate is delivered into bottle 132 from post 116 from post 116.At every end, eluate conduit 136 stops at elongated spicule 129a and 129b for the barrier film that pierces through bottle 132 and post 116 respectively.Typically, receiving flask 132 is evacuated vials, enters wherein so that the low pressure in this bottle extracts from eluant bottle 130 the eluant, eluent fluid by post 116.Independent air inlet conduit 140 fluid between eluant bottle 116 and air entry filtrator 142 is communicated with extension, so that auxiliary eluant, eluent is emptying from eluant bottle 130.Typically, receiving flask 132 is contained in its radiation shield 144 and can takes out the eluate of collection for further processing to the pharmacists with it so that screen 144 will carry the receiving flask 132 that is full of now from removing of collecting chamber 124.

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 also can use the as previously described post of other types.The present invention's imagination comprises a plurality of generators 110.As illustrating hereinafter, the present invention further imagination provides each generator alternative receiving flask of the conduit that leads to public receiving flask.In addition, the present invention imagines each generator that replacement has its eluant bottle 130, and the eluant, eluent common source can be provided, and it can be directed to any and whole generator in the generator as requested.For example, when post 116 is when having the acidic alumina column of Mo-99, eluant bottle 130 can provide source of saline solution to be used for the nucleic from this post wash-out Tc-99m.Alternatively, for example for the gel generator, the water source that is used for injection can be provided as eluant, eluent.

The present invention's imagination is fissioned or n the γ generator by the generator that the present invention uses.For example, can use the Imaging by Lantheus Medical, 331 Treble Cove Rd., N. Billerica, MA 01862, the TechneLite that USA sells

(technetium Tc99m generator).This TechneLite generator is the generator that is considered to the dry type generator, and its external source of meaning that it has a salt solusion comes elution system.Most of generators are tending towards adopting this form.Similar to other fission base generators, this TechneLite generator is convenient to the storage of Mo-99 and the subsequently separation of daughter isotope Tc-99m based on acidic alumina column.Similarly, generator 110 can comprise the Inc. by Coviden Mallinckrodt, 2703 Wagner Place, and Maryland Heights, MO 63043, the Ultra-Technekow DTE (technetium Tc-99m generator) that USA sells.This Ultra-Technekow and TechneLite unit are closely similar.In addition alternatively, Drytec (technetium Tc-99m generator) can use with the present invention.The Drytec generator is by GE Healthcare, The Grove Centre, and White Lion Road, Little Chalfont, Buckinghamshire HP7 9LL, UK sells, and similar to other fission generators listed above.

In addition, n, γ or gel generator of generator 110.A gel generator is by the India government atomic energy ministry, BRIT/BARC Vashi Complex, Sector-20 Vashi, Navi Mumbai-400 705, the Tc-99m that India sells-Geltech generator.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 structurally is different from fission type generator, still adopt similar mode to operate to use the saliferous eluant, eluent to produce Sodium Pertechnetate.Although the gel generator is not really chromatographic, term ' eluant, eluent ' will also make to describe the fluid and the term ' eluate ' that lead to generator in this article will also make to describe the fluid that leaves the gel generator with daughter nuclide in this article.

Fig. 2 describes the active decay curve of Mo-99/Tc-99m generator.Fig. 3 illustrates available activity and how to decay until reach the otiose point of generator in time.Fig. 3 is also depicted in the decay curve of the Tc-99m in the Mo-99/Tc-99m generator behind the continuous wash-out of Tc99m isotope ion.And line A describes the overall decay of parent nuclide Mo-99, and line B-D describes the growth of daughter nuclide Tc-99m, until daughter nuclide at this time wash-out so that there is not remaining approximate maximal value in the post at generator.Therefore parent nuclide will continue to decay into daughter nuclide, and the increase in the available activity of daughter nuclide is shown in time.Equation 1 is balance equation, and it describes the Mo-99 active A that exists when known before wash-out ⁰ ₁The time, the active (A of the theory T c-99m that any time behind wash-out before exists in generator ₂).

Equation (1)

λ wherein ₁The disintegration constant of Mo-99, and λ ₂It is the disintegration constant of Tc-99m.The present invention connects each the active availability of calculating in active demand and the generator.

Fig. 4 describes multigenerator elution system 200 of the present invention.Multigenerator elution system 200 comprises a plurality of generators 110.These generators 110 preferably are connected to the manifold (not shown) that comprises valve and conduit, so that corresponding individual generator becomes selectable fluid to be communicated with in the individual valve in these valves and these generators.Preferably, this manifold is connected to low pressure or vacuum source, is used for eluant, eluent is lifted by system 300.This manifold is directed to evaporating column 212 with the output of generator eluate.Eluant, eluent is directed to the generator 110 generator of selecting from the first eluant, eluent source 214, and all is directed to post 212 from the gained eluate of the generator of these selections.Evaporating column 212 will be trapped in wherein from the daughter nuclide of generator.Be conducted through evaporating column 212 from second eluant, eluent in the second eluant, eluent source 216 the daughter nuclide wash-out is entered receiving flask 218.Generator 110, post 212, eluant, eluent source 214 and 216 and receiving flask preferably be placed in the chamber 224 in radiation shield hot cell 222 so that restriction operator's exposure.

System 200 comprises control system 226 and receiving element 228.Receiving element 228 and control system 226 can be provided as the part of single computer systems.Receiving element 228 receives supply data and demand data, and control system 226 can generate with them the elution time table of generator 110, as describing Fig. 9-12.This supply data allows to calculate based on calibration data can be from each the available live vol in the generator 110, and it comprises the time and date that time and date that known initial activity and date, generator can be used for using and the first wash-out depart from.This demand data relates to the live vol of requirement and when.This demand data can be input to receiving element 328 from the module such as the ERP such as SAP or Slimline 231 automatically, or it can manually be input to receiving element 228.Control system 226 is preferably by determining which generator of wash-out and when calculating the elution time table so that with demand data and available active coupling, the waste that has minimum in order to maximize the daughter nuclide of wash-out.Then control system 226 incites somebody to action preferably, and download instruction is used for implementing wash-out to the actuating system 235 that is positioned at hot cell 222.The present invention further imagines control system 226 and can alternatively be provided in the hot cell 222, with actuating system 235 discretely or as carrying out the single computerized system of both functions.

Unrestricted by explanation, in this configuration, generator 110 is Mo99/Tc99m generator ([99Mo] molybdic acid titanium) gel generators.The first eluant, eluent source 214 preferably provides weak acid as the first eluant, eluent that is used for from generator wash-out daughter nuclide Tc-99m, although also can be used for wash-out gel generator such as the high purity waters such as sterilized water that are used for injection.Evaporating column 212 comprises that alumina adsorbant catches from the pertechnetate in the eluate of generator 110.The second eluant, eluent source 216 provides salt solusion to be used for from post 212 wash-out Sodium Pertechnetates and is collected in receiving flask 218.Then Sodium Pertechnetate can use for labelled isotope-tracer in clinical diagnosis with cold external member.

Utilize the present invention, but any combination of wash-out generator, and be collected in the post 212 from the activity of the generator of wash-out.Final radioactive concentration determined by the wash-out of evaporating column 212, its can be in very little volume wash-out.In addition, because activity can be from a plurality of generators collections and concentrated, so generator can use continuously until expire.

Referring now to Fig. 5, the alternative of multigenerator elution system 200 is shown presents.In Fig. 5, five gel generator 110a-e that are connected with valve manifold 250 are shown.Manifold 250 is preferably based on by GE Healthcare, Liege, the FASTlab that BE sells ^TMThe plug manifold that the linearity of using in the box arranges.Manifold 250 comprises 16 3 logical/3 position plug valve 1-17.Among the valve 1-17 each comprises three open ports to being close to the manifold valve and the corresponding Rule (luer) between it being opened.Each valve comprises rotatable plug, and it makes any two fluid communication with each other in the port of these three associations isolate the 3rd port in fluid ground simultaneously.The present invention further imagines plug can comprise T shape inner passage therein, stride across the valve fluid connection in order to also allow whole three ports to be placed to, but such embodiment will provide dead space, and it can require other rinsing in order to prevent the generation of the pollution of continuous fluid between flowing.Manifold 250 further comprises the first and second socket connectors 18 and 19 in its opposite end, each limits respectively vacuum ports 18a and 19a.The plug of manifold 250 and valve 1-17 and conduit described below preferably form with polymeric material, for example PP, PE, polysulfones, polyetherimide (Ultem) or polyetheretherketone (Peek).As with shown in Figure 8, although the actual number of valve is the adjustable needs that satisfy the user, manifold preferably comprises 25 3 logical/3 position plug valves.Obsolete valve can make their Rule connect by Rule accessory capping simply, and their plug is communicated with to the mobile fluid that provides between the adjacent valve.

In the connection at valve described herein place each made in the port that Rule connector by it limits.As shown in fig. 5, valve 1 supports filtering outlet 251 in its junction, Rule.Valve 2 is connected to the first eluant, eluent source 214 by slender conduit 252.The first eluant, eluent source 214 provides eluant, eluent to be used for from generator 110a-e wash-out daughter nuclide.The first eluant, eluent source 214 preferably also is connected to assist eluant, eluent to flow out towards valve 2 by conduit 252 with 233 one-tenth fluids of filtering outlet.Valve 3 is connected to the second manifold 256 by slender conduit 254, and the open of eluant, eluent passage 118 that is provided to generator 110a-e connects.That is, can have its eluant, eluent source although the present invention also imagines each generator as illustrated in fig. 1, the present invention preferably provides each that the single source of eluant, eluent is used for the wash-out generator.The eluate passage 120 of generator 110a-e connects back manifold 250 by slender pipeline 260a-e respectively.Conduit 260a-e extends between valve 4-8 at the corresponding eluate passage 120 of generator 110a-e respectively.

Valve 9 is connected to the input port of evaporating column 212 by slender pipeline 262, so that bootable to post 212 from the eluate of generator.Valve 10 is connected to the second eluant, eluent source 216 by slender conduit 264.The second eluant, eluent source 216 provides eluant, eluent to come from post 212 wash-out daughter nuclides.The second eluant, eluent source 216 is preferably gone back fluid and is communicatively connected to filtering outlet 263 and assists the second eluant, eluent to flow out towards valve 9 by conduit 256. Valve 11 and 12 is by Rule accessory capping, and their plug is orientated to provide the Fluid Flow in A that passes through it between valve 10 and 13.Valve 13 is connected to the input port 268 of receiving flask 218 by slender conduit 266, makes it possible to guide product fluid wherein.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 preferably is 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.

Now the example wash-out will be described.Calculated the elution time table, it requires from generator 110a and 110c wash-out active.By apply vacuum (that is, enough low pressure) at port one 9a, the first eluant, eluent will extract from the first source 214.Valve 1-17 is set so that the first eluant, eluent flow through valve 2 and 3 and conduit 254 enter manifold 256.At first, valve 5-8 being set allows to flow through conduit 260a to valve 9 from the eluate of generator 110a.Valve 9 these eluates of guiding flow through conduit 262 to the input port of post 212.Eluate will extract by valve 15 to valve 14 and enter waste material bottle 219 from post 212.The volume of waste material bottle 219 will enough be collected the whole of the liquid carried from post 212.Then the plug of changeover valve 4 is isolated generator 110a, and the rotation of the plug of valve 6 enters generator 110c so that the first eluant, eluent will extract from the second manifold 256.Then eluate from generator 110c is guided through valve 6-8 to valve 9.Valve 9 guiding eluates flow through conduit 262 to the input port of post 212.Eluate will extract by valve 15 to valve 14 and enter waste material bottle 219 from post 212.Thereby the daughter nuclide from generator 110a and 110c is collected in the evaporating column 212.

For from post 212 wash-out daughter nuclides, valve 10 will be arranged under the suction of port one 9a will be from second eluant, eluent in source 264 by conduit 264 and towards valve 9 guiding.The second eluant, eluent extracts by conduit 262 by the input port of post 212 and by post 212.When leaving post 212 and enter valve 15, post 212 eluates will comprise daughter nuclide and be used for allotting and enter receiving flask 218.This eluate will be directed to valve 13 and enter bottle 218 by conduit 266, apply by valve 17 and conduit 276 from the suction of port one 9a.Bottle 218 is then removable or release and provide daughter nuclide for further being processed by the pharmacists.Enter identical receiving flask or be combined in addition with from the not use eluate of allotting before from thereby the allocation of generator is bootable subsequently because control system 226 it be used for comprised any remaining activity so that the requirement of the data that satisfy the demands from the calculating of generator 110a-e allocation.

Manifold 250 preferably forms and is attached to actuating system 235, its joint and arrange valve plug orientation and provide low-pressure suction or vacuum is used for withdrawn fluid by this manifold and enters bottle.Actuating system 235 comprises rotatable arm, each in the plug of its engage valve 1-17 and can in wash-out operation each be placed in the orientation of expectation.Actuating system 235 also comprises a pair of sleeve pipe according to the present invention, and wherein each engages one that port 18a is connected with 19a and becomes Fluid Sealing to connect to provide low pressure or vacuum source to manifold 250.Preferably, manifold 250 is attachable to FASTlab ^TM(by GE Healthcare, Liege, BE sells) synthesizer, its sequencing comes operated valve and applies vacuum.Because the FASTlab compositor has been designed to operate in the environment of hot cell, it is ideally suited the actuating device as system 200.Actuating system 235 is moved according to the elution time table commander who calculates by control system 226.

Fig. 6 and 7 describes the multigenerator elution system 300 of alumina base Mo99 generator 110.Multigenerator elution system 300 comprises a plurality of generators 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 preferably is connected to the manifold (not shown) that comprises valve and conduit, so that corresponding individual generator becomes selectable fluid to be communicated with in the individual valve in these valves and these generators.This manifold is directed to cation seperation column 315 with the output of generator eluate.The generator eluate flows through this cation seperation column 315 and then enters evaporating column 312.Preferably, this manifold is connected to vacuum source for eluant, eluent is lifted by system 300.This cation seperation column is not used in bottles up daughter nuclide and comprises suitable medium and be used for removing competing ions, and it adversely disturbs evaporating column.Thereby eluant, eluent is directed to the generator 110 generator of selecting from the first eluant, eluent source 314 in system 300, and all is guided through post 315 and to post 312 from the gained eluate of the generator of these selections.Evaporating column 312 will be trapped in wherein from the daughter nuclide of generator.Be conducted through evaporating column 312 from second eluant, eluent in the second eluant, eluent source 316 the daughter nuclide wash-out is entered receiving flask 318.Generator 110, post 312, eluant, eluent source 314 and 316 and receiving flask preferably be placed in the chamber 324 in radiation shield hot cell 322 so that restriction operator's exposure.

System 300 comprises control system 326 and receiving element 328.Receiving element 328 and control system 326 can be provided as the part of single computer systems.Receiving element 328 receives supply data and demand data, and control system 226 can generate with them the elution time table of generator 110, as describing Fig. 9 and 10.This supply data allows to calculate based on calibration data the live vol of each acquisition that can be from generator 110, and it comprises the time and date that time and date that known initial activity and date, generator can be used for using and the first wash-out depart from.This demand data relates to the live vol of requirement and when.This demand data can be input to receiving element 328 from the ERP such as the electronics such as SAP or Slimline module 331 automatically, or it can manually be input to receiving element 328 by the operator.Control system 326 is preferably by determining which generator of wash-out and when calculating the elution time table so that with demand data and available active coupling, the waste that has minimum in order to maximize the daughter nuclide of wash-out.Then control system 326 incites somebody to action preferably, and download instruction is used for implementing wash-out to the actuating system 335 that is positioned at hot cell 322.The present invention further imagines control system 326 and can alternatively be provided in the hot cell 322, with actuating system 335 discretely or as carrying out the single computerized system of both functions.

In this configuration, the first eluant, eluent source 314 preferably provides acid salt or weak acid (typically salt solusion) as the first eluant, eluent that is used for from generator wash-out daughter nuclide Tc-99m.Because the first eluant, eluent is salt solusion, so cation seperation column 315 at first is used for removing sodion in order to allow to be concentrated in evaporating column 312.Evaporating column 312 comprises that alumina adsorbant catches from the pertechnetate in the eluate of generator 110.The second eluant, eluent source 316 provides salt solusion to be used for from post 312 wash-out Sodium Pertechnetates and is collected in receiving flask 318.Then Sodium Pertechnetate can use for labelled isotope-tracer in clinical diagnosis with cold external member.

Utilize the present invention, but any combination of wash-out generator, and from the activity of the generator of wash-out by post 315 and be collected in the post 312.The twin columns method allows the generator based on fission Mo-99 and aluminium oxide technology to utilize the odds for effectiveness of concentrator of the present invention system.Final radioactive concentration determined by the wash-out of evaporating column 312, its can be in very little volume wash-out.In addition, because activity can be from a plurality of generators collections and concentrated, so generator can use continuously until expire.

Referring now to Fig. 7, the alternative of multigenerator elution system 300 is shown presents.In Fig. 7, five gel generator 110a-e that are connected with valve manifold 350 are shown.Manifold 350 is preferably based on by GE Healthcare, Liege, the FASTlab that BE sells ^TMThe plug manifold that the linearity of using in the box arranges.Manifold 350 comprises 16 3 logical/3 position plug valve 1-17.Among the valve 1-17 each comprises that this Rule port is between other relative ports to three open ports that are close to the manifold valve and the corresponding Rule that is located thereon is opened.Each valve comprises rotatable plug, and it makes any two fluid communication with each other in the port of these three associations isolate the 3rd port in fluid ground simultaneously.The present invention further imagines plug can comprise T shape inner passage therein, stride across the valve fluid connection in order to also allow whole three ports to be placed to, but such embodiment will provide dead space, and it can require other rinsing in order to prevent the generation of the pollution of continuous fluid between flowing.Manifold 350 further comprises the first and second socket connectors 18 and 19 in its opposite end, each limits respectively vacuum ports 18a and 19a.The plug of manifold 350 and valve 1-17 and conduit described below preferably form with polymeric material, for example PP, PE, polysulfones, polyetherimide or polyetheretherketone.As with shown in Figure 8, although the actual number of valve is the adjustable needs that satisfy the user, manifold preferably comprises 25 3 logical/3 position plug valves.Obsolete valve can make their Rule connect by Rule accessory capping simply, and their plug is communicated with to the mobile fluid that provides between the adjacent valve.

In the connection at valve described herein place each is connected to the port, Rule that is limited by its Rule connector and makes.As shown in Figure 8, valve 1 supports filtering outlet 351 in its junction, Rule.Valve 2 is connected to the first eluant, eluent source 314 by slender conduit 352.The first eluant, eluent source 314 provides eluant, eluent to be used for from generator 110a-e wash-out daughter nuclide.The first eluant, eluent source 314 preferably also is connected to assist eluant, eluent to flow out towards valve 2 by conduit 352 with 333 one-tenth fluids of filtering outlet.Valve 3 is connected to the second manifold 356 by slender conduit 354, and the open of eluant, eluent passage 118 that is provided to generator 110a-e connects.That is, can have its eluant, eluent source although the present invention also imagines each generator as illustrated in fig. 1, the present invention preferably provides each that the single source of eluant, eluent is used for the wash-out generator.The eluate passage 120 of generator 110a-e connects back manifold 350 by slender pipeline 360a-e respectively.Conduit 360a-e extends between valve 4-8 at the corresponding eluate passage 120 of generator 110a-e respectively.

Valve 9 is connected to the input port of cation seperation column 315 by slender pipeline 362.Cation seperation column 315 is served before concentrated always, and the eluate from generator removes competing ions.Valve 10 is connected to the second eluant, eluent source 316 by slender conduit 364.The second eluant, eluent source 316 provides eluant, eluent to come from post 312 wash-out daughter nuclides.The second eluant, eluent source 316 also preferably fluid be communicatively connected to filtering outlet 363 and assist the second eluant, eluent to flow 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, in order to can guide product fluid wherein.Valve 15 is connected to the output port of post 312, so that post 312 preferably is 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.

Now the example wash-out will be described.Calculated the elution time table, it requires from generator 110a and 110c wash-out active.By apply vacuum (that is, enough low pressure) at port one 9a, will extract the first eluant, eluent from the first source 314.Valve 1-17 is set so that the first eluant, eluent flow through valve 2 and 3 and conduit 354 enter manifold 356.At first, valve 5-8 being set allows to flow through conduit 360a to valve 9 from the eluate of generator 110a.Valve 9 these eluates of guiding flow through conduit 362 to the input port of cation seperation column 315.Eluate will extract by valve 12 and enter the ingress port that slender conduit 265 enters evaporating column 312 from post 315.Waste material will continue to extract by post 312 by valve 15 down to valve 13 and enter waste material bottle 319.The volume of waste material bottle 319 will enough be collected the whole of the liquid carried from post 315.Then the plug of changeover valve 4 is isolated generator 110a, and the plug of changeover valve 6 enters generator 110c so that the first eluant, eluent will extract from the second manifold 356.Then eluate from generator 110c is guided through valve 6-8 to valve 9.Valve 9 guiding eluates flow through conduit 362 to the input port of post 315.Eluate will extract by valve 12 and enter the ingress port that slender conduit 265 enters evaporating column 312 from post 315.Waste material will continue to extract by post 312 by valve 15 down to valve 13 and enter waste material bottle 319.Thereby the daughter nuclide from generator 110a and 110c is collected in the evaporating column 312.

For from post 312 wash-out daughter nuclides, valve 10 will be arranged in guiding under the suction of port one 9a from second eluant, eluent in source 316 by conduit 364 and towards valve 12.The second eluant, eluent extracts by conduit 365 by the input port of post 312 and by post 312.When leaving post 312 and enter valve 115, post 312 eluates will comprise daughter nuclide and be used for allotting and enter receiving flask 318.This eluate will be directed to valve 14 and enter bottle 318 by conduit 366, apply by valve 17 and conduit 376 from the suction of port one 9a.Bottle 318 is then removable or release and provide daughter nuclide for further being processed by pharmacists or technician.Enter identical receiving flask or be combined in addition with from the not use eluate of allotting before from thereby the allocation of generator is bootable subsequently because control system 326 it be used for comprised any remaining activity so that the requirement of the data that satisfy the demands from the calculating of generator 110a-e allocation.

Manifold 350 forms and is attached to actuating system 335, its joint and arrange valve plug orientation and provide low-pressure suction or vacuum is used for withdrawn fluid by this manifold and enters bottle.Actuating system 335 comprises rotatable arm, each in the plug of its engage valve 1-17 and can in wash-out operation each be placed in the orientation of expectation.Actuating system 335 also comprises a pair of sleeve pipe according to the present invention, and wherein each one of engaging that port 18a is connected with 19a becomes Fluid Sealing to connect and provides low pressure or vacuum source to manifold 350.Preferably, manifold 250 is attachable to FASTlab ^TM(by GE Healthcare, Liege, BE sells) synthesizer, its sequencing comes operated valve and applies vacuum.Because the FASTlab compositor has been designed to operate in the environment of hot cell, it is ideally suited the actuating device as system 300.Actuating system 335 is moved according to the elution time table commander who calculates by control system 326.

Referring now to Fig. 8, the wash-out box 400 that the multigenerator elution system is used together is shown.In Fig. 8, be used for four aluminium oxide generator 110a-d with decay Mo-99 generation Tc-99m and illustrate with valve manifold 450 and be connected.Box 400 comprises the container 402 with smooth antetheca 404, and this antetheca 404 is demarcated by the perisporium 406 that limits container chamber 408.Box 400 is support elongated manifold 450 in the chamber 408 of adjacent bottom wall 406a.Manifold 450 is preferably based on by GE Healthcare, Liege, the FASTlab that BE sells ^TMThe plug manifold that the linearity of using in the box arranges.Manifold 450 comprises 25 3 logical/3 position plug valves 1 '-25 '.In the valve 1 '-25 ' each comprises that this Rule port is between other relative ports to three open ports that are close to the manifold valve and the corresponding Rule that is located thereon is opened.Each valve comprises rotatable plug, and it makes any two fluid communication with each other in the port of these three associations isolate the 3rd port in fluid ground simultaneously.The present invention further imagines plug can comprise T shape inner passage therein, stride across the valve fluid connection in order to also allow whole three ports to be placed to, but such embodiment will provide dead space, and it can require other rinsing in order to prevent the generation of the pollution of continuous fluid between flowing and wherein be trapped in flow losses in the dead space.Manifold 450 further comprises the first and second socket connectors 26 and 27 in its opposite end, each limits respectively vacuum ports 26a and 27a.The plug of manifold 450 and valve 1 '-25 ' and guide coupling described below preferably form with polymeric material, for example PP, PE, polysulfones, polyetherimide or polyetheretherketone.As with shown in Figure 8, although the actual number of valve is the adjustable needs that satisfy the user, manifold preferably comprises 25 3 logical/3 position plug valves.Obsolete valve can make their Rule connect by Rule accessory capping simply, and their plug is communicated with to the mobile fluid that provides between the adjacent valve.

Box 400 is versions of pre-assembled synthetic box, and it is designed to be adapted to install and clinical batch that is connected synthetic different radioactive drugs with minimum client.Box 400 preferably adopts kit form to provide, and this external member has and will be connected to generator, bottle and eluant, eluent source or a plurality of source according to the present invention and be used for the whole of the connector of the duct conduits of wash-out nucleic and support and filtrator.Preferably, box 400 offers the user, has wherein made conduit to each connection in Rule of its valve, so that only free end need to closely cooperate with suitable parts.The box that provides like this can be assembled under aseptic condition and pack, if so that suitably opening and will keep suitable aseptic level for pharmaceutical operations in the clean environment.

In the connection at valve described herein place each made in the port, Rule that Rule connector by it limits.As shown in Figure 8, 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 the wash-out operation or provide as required rinse fluid to be used for rinsing manifold 250.Rinse streams body source 415 preferably also is connected to assist eluant, eluent to flow out towards valve 4 ' by conduit 452 with 433 one-tenth fluids of filtering outlet.Namely, although imagining box 400, the present invention can provide each the single eluant, eluent source that is used for the wash-out generator as in Fig. 5 and 8, describing, in the embodiment of Fig. 8, the present invention includes each generator with its eluant, eluent source (being provided in the eluant bottle 130) as illustrated in fig. 1.Each generator that eluant, eluent source 130 with it is provided is preferably in order to prevent risk from the excess dilution of the eluate volume of public reservoir.In addition, by each generator in the attached wash-out source with it is provided, a plurality of in the manifold valve 5 '-14 ' will can be used for being connected to generator.Air out on the manifold is used for bleeding off too much or obsolete vacuum.The eluate passage 120 of generator 110a-d connects back manifold 450 by slender pipeline 460a-d respectively.Conduit 460a-d arrives extension between the valve 15 '-18 ' at the corresponding eluate passage 120 of generator 110a-d respectively.

Valve 5 '-14 ' each by Rule accessory capping, this accessory seals Rule port of each valve.Valve 5 '-14 ' can be used for scaling up box 400 and holds other generator (just in case the 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 before concentrated always, and the eluate from generator removes competing ions.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, eluent source 416 by slender conduit 464.The second eluant, eluent source 416 provides eluant, eluent to come from evaporating column 412 wash-out daughter nuclides.The second eluant, eluent source 416 also preferably fluid be communicatively connected to filtering outlet 463 and assist the second eluant, eluent to flow out towards valve 22 ' by conduit 462.Valve 24 ' is connected to the output port of post 412, so that post 412 preferably is directly connected to valve 24 '.

To be described to now the waste material bottle and be connected connection with receiving flask.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.

Now the example wash-out will be described.Calculated the elution time table, it requires from generator 110b and 110d wash-out active.By apply vacuum (that is, enough low pressure) at port 26a, the first eluant, eluent will extract for generator 110b from the first source bottle 130.Valve 1 '-25 ' is set so that the first eluant, eluent flows through generator 110b, passes through conduit 460b to valve 16 ' and by arriving valve 19 '.Valve 19 ' guiding eluate flows through conduit 462 to the input port of cation seperation column 415.Eluate will extract by valve 21 ' and enter the ingress port that slender conduit 465 enters evaporating column 412 from post 415.Waste material will continue to extract by post 412 by valve 24 ' down to valve 23 ' and enter waste material bottle 419.Thereby the volume of waste material bottle 419 will enough be collected the whole of the liquid carried from post 412.

Then the plug of changeover valve 16 ' is isolated generator 110b, and the plug of changeover valve 18 ' is so that the first eluant, eluent will be from bottle 130 extractions that are connected to generator 110d.Then eluate from generator 110d is guided through conduit 460d to valve 18 ' and then arrives forward valve 19 '.Valve 19 ' guiding eluate flows through conduit 462 to the input port of post 415.Eluate will extract by valve 21 ' and enter the ingress port that slender conduit 465 enters evaporating column 412 from post 415.Waste material will continue to extract by post 412 by valve 24 ' down to valve 23 ' and enter waste material bottle 419.Thereby the daughter nuclide from generator 110b and 110d is collected in the evaporating column 412.

For from post 412 wash-out daughter nuclides, valve 22 ' will be arranged in guiding under the suction of port 26a from second eluant, eluent in source 416 by conduit 464 and valve 22 ' and towards valve 21 '.The second eluant, eluent extracts by conduit 465 by the input port of post 412 and by post 412.When leaving post 412 and enter valve 24 ', post 412 eluates will comprise daughter nuclide and be used for allotting and enter receiving flask 418.This eluate will be directed to valve 25 ' and enter bottle 418 by conduit 466, apply by valve 1 ' and conduit 476 from the suction of port 26a.Bottle 418 is then removable or release and provide daughter nuclide for further being processed by the pharmacists.Enter identical receiving flask or be combined in addition with from the not use eluate of allotting before from thereby the allocation of generator is bootable subsequently because control system of the present invention it be used for comprised any remaining activity so that the requirement of the data that satisfy the demands from the calculating of generator 110a-d allocation.

Box 400 forms and is attached to actuating system, its joint and arrange valve plug orientation and provide low-pressure suction or vacuum is used for withdrawn fluid by manifold and enters bottle.Actuating system comprises rotatable arm, each in the plug of its engage valve 1 '-25 ' and can in wash-out operation each be placed in the orientation of expectation.Actuating system also comprises a pair of sleeve pipe according to the present invention, and wherein each one of engaging that port 26a is connected with 27a becomes Fluid Sealing to connect and provides low pressure or vacuum source to manifold 450.Preferably, manifold 450 is attachable to FASTlab ^TM(by GE Healthcare, Liege, BE sells) synthesizer, its sequencing comes operated valve and applies vacuum.Because the FASTlab compositor has been designed to operate in the environment of hot cell, so it is ideally suited the actuating device as box 400, the actuation instructions that receives it from control system is come according to the elution time table handling of calculating.

For all embodiment (being included in those that describe in detail among Fig. 5,7 and 8) of box of the present invention and manifold system, box or manifold preferably are attachable to the FASTlab device.The all liq transmission is undertaken by the vacuum that applies (or low pressure).Be envisioned for via standard Luer to all connections of manifold box and lock.The conduit that is used for being connected to generator preferably is to allow with the silicone tube road that barrier film stops that the place, corresponding port on generator 110 penetrates by spicule 125a and 129a.Be attached at eluant bottle 130 in the situation of generator, but Application standard connects.Thereby generator does not need to revise to work with the present invention.

For all embodiment, the external source of rinse fluid (for example water for injection (WFI)) also can be connected to manifold and be used for cleaning and rinsing purpose in addition.When wash-out gel generator, the WFI source can be connected to each generator and also play the first eluant, eluent.As for the more special description of Fig. 8, the present invention imagines the first eluant, eluent can or be connected respectively to each generator " wash-out bottle " from reservoir or pre-xylometer.Prediction source is desirable in order to prevent the excess dilution of eluate volume and discharge the other manifold valve that is used for being connected to generator.Air out on the manifold is used for bleeding off too much or obsolete vacuum.

The present invention further imagines for some embodiment, the wash-out chemistry that depends on requirement, the first source (as describing for Fig. 5 and 7) that is directly connected to the eluant, eluent of manifold can be used for wash-out generator and evaporating column, thereby avoids the needs to the second source of the eluant, eluent that will be connected to manifold.For example, if the system of Fig. 7 300 adopts aluminium oxide generator and aluminium oxide evaporating column, the first source that the present invention imagines eluant, eluent can provide salt solusion, and it is used for the wash-out generator and is used for the wash-out evaporating column.

Cation seperation column is used for removing such as competing ions such as chlorides from eluate.In certain embodiments, the pertechnetate ion current is crossed cation seperation column and the acidifying alumina column of be captured to it forward (concentrating) here.Allow liquid to flow through post and enter the garbage collection container to supply to process in the future.Acidifying alumina column (as mentioned statement) is used for catching and concentrated pertechnetate ( ^99mTc).Although pertechnetate catches at alumina column, liquid (being water basically) removes and is collected in the waste material container by the bottom of vacuum from post.In case concentration step is finished, alumina column preferably adopts with the current identical mode of fission generator with small size salt solusion wash-out pertechnetate basically as Sodium Pertechnetate [Na ^99mTcO _4-] remove, and be collected in the collection of products bottle.

With reference to Fig. 9, user demand data of the present invention and supply data are determined and are carried out the maximal efficiency utilization of parent-daughter generator group in radiopharmaceutical operation.This supply data allows the robotization at any given time of (daughter nuclide) available live vol to calculate.Generator is sold and is had an activity of known quantity.This supply data can obtain from generator bar code or artificial data input.This demand data is to satisfy the live vol of customer order in the special time requirement.Data can be via electric transmission from such as SAP or Slimline(or equivalent) etc. the ERP software system, or by artificial input.Typically, in the radiopharmaceutical environment, customer order is divided into the conveying that is ranked some time of one day to carry out.

The present invention relatively demand activity requires and available at any given time activity.In addition, system will attempt the plan of configuration generator wash-out and propose to represent for the best-fit scheme from the optimum efficiency of given generator wash-out.In case this best-fit scheme calculates, the operator has some options: a) carry out the wash-out plan of being determined by system, b) manually reconfigure wash-out plan-allow system-computed and to operator's display effect, or c) simulate ' what-if scene ' by the elution time table of inputting some demand requirement and/or supply data and looking back the calculating of under the constraint of input, being determined by system.

When the wash-out plan of confirming from the operator to calculate when being acceptable, the present invention sends data to actuating system and comes the generator selected according to elution time table wash-out.Eluate from the generator of selecting all is concentrated to for example Tc-99m on the alumina column by box.In case all generator wash-outs are finished, alumina column is wash-out in the eluant, eluent (typically 5-6mL) of for example salt solusion of wanting cube.In case this operation is finished, control system is upgraded activity data with the variation of any requirement, recomputates growth and upgrades the elution time table.

Generally, ERP system is that integrated computer based is used, and it is used for managing internal and external resource, comprises tangible assets, financial resources, material and human resources.Its purpose is to be convenient to information flowing between all business functions in the scope of tissue, and management is to external stakeholders's connection.Be based upon on the centralized data base and the public computing platform of general using, ERP system merges all business operations the system environments that enters unified and enterprise-wide.ERP system can reside on the centralized server, or cross-module blocking hardware and software cell distribution, and it provides " service " and communicates by letter in LAN (Local Area Network).Distributed Design allows assembling need to not place in the zone of the whole abilities that will not use them a plurality of duplicate of complicated and expensive computer system from the business of different suppliers' module.

Thereby method of the present invention comprises input step 610, and wherein the supply data of each in the generator is input to the receiving element of elution system.Then the method comprises that input is from how many activity of a plurality of generator requirements and the second step 620 of demand data when to receiving element.This heel calculates and selects step 630, wherein determines each suitable time of eluent table in a plurality of generators according to the demand data of the supply data of input and input.This calculating and select step 630 preferably relatively more active current demand, active future demand and at present and the activity that can use from generator in subsequently demand point or elution time, and select with which generator of wash-out with when in order to minimize the waste of the daughter nuclide that in the data that satisfy the demands, is produced by generator.Yet, have elution step 670, wherein the generator wash-out of daughter nuclide from selecting.

Step 610 further comprises the calibration data (the typically activity of each generator and date) 612 of inputting each generator, input generator can with time and date 614 and the step of inputting the time and date that the first wash-out departs from from the reference time.Step 612,614,616 can manually be carried out to receiving element from each the information in these steps by artificial input, and such information generally offers each generator.Alternatively, step 612,614 and 616 can or automatically be carried out by the such information electronic ground of the bar code scanning that is subordinated to each generator.Equally, step 620 can manually or electronically be carried out, and wherein demand data is generally by the ERP system supply.For manually carry out step 620, the operator will obtain demand data information and it will be input to receiving element.Preferably, when artificial input demand data, receiving element or control system will be compiled into the demand data collection to information, although the operator also can carry out this compiling before input amounts to demand data.Alternatively, ERP system can be communicated by letter with receiving element electronically so that individual order automatically is input to the elution time table of system and calculating.

The present invention further imagines the step 618 that step 610 can comprise input given data constant.Step 618 can be provided for considering such data constant in step 630.These data constants preferably comprise mark, the parent-balance equation of daughter activity and the time expiration of generator of parent nuclide half life period and decay equation, daughter nuclide half life period and decay equation, wash-out output efficiency, parent nuclide available wash-out in decaying.

Step 630 comprises preferably adopting such as the fixed intervals such as 30 minutes calculates 632 and show the step of the available activity of 634 each generator.Preferably, calculation procedure 632 adopts equations (1) and step display 634 to show activity in each generator with the interval of calculating.In addition, step 630 can comprise that the broad sense reduction gradient algorithm of the activity level that carries out demand data and a plurality of generators analyzes to determine that the suitable time of eluent table is used for minimum waste.Alternatively, the operation of step 630 imagination is from the simulation of the various elution time tables of a plurality of generators, and selection causes the elution time table of the daughter nuclide waste of minimum when satisfying the demands data.In addition, the method preferably is included in the step 638 that shows demand data on the interval identical with supply data.Step 630 preferably further comprises the step 638 of calculating best-fit elution curve or timetable, be used for to select and which of generator will adopt the possible efficient way data that satisfy the demands at wash-out preset time with, thereby maximize useful life longevity and the minimum waste of each generator.Then the method can comprise provides the step 640 of elution time table to the operator.

Preferably, the demonstration of elution time table is provided at the upper and method of graphic user interface (GUI) and comprises that giving the operator is used for the step 642 that wash-out in preset time makes the invalid option of the optimization elution time table of calculating by the different generator that replaces being ranked.If operator's refusal makes system invalid, then method will advance to and send the wash-out instruction to the step 660 of actuating system.If the operator selects to make the wash-out instruction ignore from step 638, method comprises that further the artificial input of operator is to the step 644 of the modification of elution time table.Step 644 allows the operator when to select with the specific generator of wash-out.Then method comprises and recomputates elution time table 646 and show active availability that each generator upgrades in time and the step 648 of the time that is ranked of each wash-out from generator.Consider any other operator constraint, step 646 preferably adopts the algorithm identical with step 630 in determining the suitable time of eluent table.Then method comprises the step 650 of the elution time table that prompting operation person accepts to upgrade.If the elution time table that the operator accepts to upgrade will provide suitable instruction to be used for generator wash-out, step 660 to actuating system with elution time table and control system are set.If the operator does not accept the elution time table that upgrades, method with repeating step 644,646 and 648 until the operator accepts the elution time table.In case the elution time table that upgrades is satisfied for the operator, method will advance to step 660.

After step 660, actuating system will carry out step 670, and according to elution time table wash-out generator.Step 642,644,646,648 and 650 provides ' operator is in loop ' option to monitor and manages wash-out from generator, and allows the operator to make the timetable of calculating invalid.Under any circumstance, need not the operator thereby the present invention can operate and intervene and can automatically be ranked wash-out and do not have the operator to input timetable one time, make thus the operator free to turn to other pharmacy responsibilities.Yet, think that it is desirable in order to accept the elution time table that certain point in circulation provides the operator.

After elution step 670, method can comprise the step 672 of the generator selected of having confirmed wash-out.In addition, if method preferably comprises the activity data that recomputates in active growth 674, the modify steps 632 and needs then repeating step 638 and following step recomputate best-fit elution time table for satisfying the demands data.

The present invention further provides for managing from the computer program of the wash-out of multigenerator elution system according to the present invention.The present invention further provides the multigenerator elution system, it comprises be used to the computer hardware of carrying out computer program of the present invention.This computer program comprises computer usable medium, and it has be used to the computer usable program code of carrying out method of the present invention.This computer program code comprises computer usable medium, and it has the computer usable program code of management multigenerator elution system.The computer program that comprises computer usable program code receive from generator many parents-daughter generator input supply data and to the demand data from the activity of generator.Computer program further comprises: computer usable program code, and it is based on the elution time table that can calculate with active and demand data generator in the generator; And computer program code, it is according to the generator wash-out of actuating system to select from generator of this elution time table guiding elution system.

Computer program preferably further comprises for the available activity that shows supply data, demand data, generator and at least one the computer program code in the elution time table.In addition, this computer program code that calculates the elution time table also comprises the computer program code of analyzing to be identified for the optimization elution time table of minimum waste be used to the broad sense reduction gradient algorithm of the activity level that carries out demand data and a plurality of generators.Alternatively, the computer program code that be used for to calculate the elution time table also comprises for operation from the simulation of the various elution time tables of a plurality of generators and the computer program code of selecting to cause the elution time table that the daughter nuclide of minimum wastes when satisfy the demands data.Computer program preferably also comprises for allowing the operator by inputting the new invalid computer program code of elution time table that computer program makes calculating that is tied to, and the computer program code that is used for calculating based on these new constraints new elution time table.In addition, computer program preferably comprises for storing supply data, demand data and elution time table for the computer program code of in the future retrieval and can being the purpose service that record maintenance or record support keep.

Figure 10 describes for the screenshotss that the graphic user interface of the present invention (GUI) of supply data information is provided to multigenerator elution system of the present invention.Figure 10 illustrates supply data entr screen 700.Screen 700 provides Microsoft Excel

Screen, it is illustrated in the supply data of six generators listing among row A, the row 6-11.The reference time that row B, row 6-11 list each generator.First wash-out of each departs from (in hour) in the generator that row C, row 6-11 have listed.The clauses and subclauses that lack will be considered as zero offset.Row D, row 6-11 list the initial activity of each generator in the reference time.Row E, row 6-11 have listed each generator and when can be used for using.As the bug check to the data clauses and subclauses, the reference time of row among the A must be can be used for before at least ten two hours of service time among the 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 the wash-out output efficiency, and typically about 0.83.

Figure 11 is provided by the screenshotss of the GUI of the present invention of the elution time table that calculates be used to six generators that provide Figure 10.Figure 10 illustrates wash-out management window 800, and it provides supply data, demand data and the elution time table of multigenerator elution system.This is based on worksheet or the best-fit result of demand balance efficiency and the needs of activity in the future.Although the feature of the relevant information in Figure 11 display line 46 to 69, it represents from 9:30 in the morning on the 12nd 10 o'clock to 2010 July of afternoon on July 11st, 2010, and the information of window 800 continues at the generator life period, typically two weeks and can rolling.Row A, row 46 to 69 provide interval time, and the calculating of this interval time and allocation occured during the period that illustrates.Provide the time interval with 30 minutes intervals.Row D, row 46 to 69 are listed the time that data distribution according to demand must occur.Time of listing considers to make behind the wash-out nucleic with the state of the expectation processing time to the desired state of user.Thereby for example, row D illustrates wash-out will be in the 12:00 in the morning on Monday on July 12nd, 2010, the morning 2:00, the morning 4:00 and 7:00 operation in the morning.Further be rolled to unsighted be about to illustrate after a while demand and other information of time downwards.Row E provides the balance residue from untapped any previous wash-out, and advances in time decay is shown.Row F, P, Z, AJ, AT and BD mark respectively for the generator wash-out of being expert at 1, list among row G, Q, AA, AK, AU and the BE and when are ranked.In corresponding generator wash-out, numeral ' 1 ' is input to row F, P, Z, AJ, AT and BD in activity.As can be seen, for the generator of each wash-out, the next line behind the wash-out illustrates the activity of much less, behind its indication wash-out, active growth occurs.

As being listed as shown in D, the row 50, in the demand of existence at midnight (row 50) for 14,350mCi activity.Control system is calculated for the best satisfies whole in the known demand among the row D, and generator 1 and generator 5 satisfy this demand with wash-out, and the not use surplus of 27mCi is provided, and it can include the wash-out in future in.Similarly, wash-out (row 54) at 2:00 in the morning, in order to satisfy for 15, the demand of 931mCi activity, 2405.5mCi activity will be from generator 2 wash-outs, the activity of 2405.5mCi will be from generator 3 wash-outs, and 11,120.5mCi activity will from generator 4 wash-outs, provide the not use surplus of 22mCi.Therefore also will be included in this wash-out from the remaining activity of wash-out before, current wash-out can be can't help the demand that their own totals obtain listing in some instances.

The operator can be by being listed as deletion ' 1 ' and selecting another generator to come to make the elution time table that provides invalid from its wash-out from wash-out.Control system will refill that clauses and subclauses in the window 800 illustrate new elution time table and in each preset time each generator available activity, in the demand of each elution time and any surplus in the remaining activity.Simulation feature of the present invention for example allows to impact when occuring when supply, and the present invention is for the impact of assessment " what-if " scene and carry maximum dosage particularly useful for given supply situation at last.Under any circumstance, when the operator is satisfied with to elution time, can stay alone its as shown automatically operation.Utilize the wash-out that automatically carries out, the operator will be free other responsibilities that turns to.In addition, software provides the record of the wash-out that carries out, and simplifies record and keeps purpose.In addition, although supply data screen 700 and wash-out management window 800 are followed the tracks of six generators, the present invention is adjustable, and wherein it can be monitored and the as many generator that is included in the multigenerator elution system.

The present invention can the radiotropism pharmacy provide cost savings.The Largest Single Item cost of radiopharmaceutical is the Tc-99m/Mo99 generator, and it is used for consisting of " cold external member " (diagnostic reagent).With the action of experienced radiopharmacist test average pharmacy generator efficiency being shown is 65-68%.Av eff stably was elevated to 98-100% after new tool was realized.Typically, on average one week of pharmacy can consume four 18Ci generators.Each generator has the useful preservation life-span in two weeks.Thereby on basis weekly, pharmacy will need to manage eight generators by their decay and use circulation.Current, use weekly four 18Ci unit with $ 7000, each is the cost of annual $ 1.456MM.If identical pharmacy the application of the invention brings up to 100% with its efficient from 65%, annual cost reduces about $ 0.5MM.

Although illustrated and described the particular embodiment of the present invention, it will be obvious can making a change and revise and do not depart from instruction of the present invention for those skilled in that art.The purport of setting forth in description in front and the accompanying drawing only provides by explanation and not conduct restriction.Actual range of the present invention is intended to limit in these claims when checking following claim all sidedly when objective based on prior art.

Claims (59)

1. multigenerator elution system comprises:

A plurality of generators;

The eluant, eluent source;

Control system, be used for following the tracks of each activity of described a plurality of parent-daughter nucleus generator, receive the demand data of the active requirement that produces of indication, described control system is configured to come generator that wash-out selects from described a plurality of generators in order to the desired amount of daughter isotope is provided with the first eluant, eluent;

Receiving element, be used for receiving supply data and demand data, wherein said supply data comprises the information that allows to calculate the available activity in the described generator, and described demand data further comprises at least the amount of the daughter nuclide that will produce and produces the timetable of the amount of described daughter nuclide, described receiving element can operate with described control system, and described daughter nuclide satisfies the demand of described demand data representative from the described wash-out of described a plurality of generators so that control system will be ranked;

Evaporating column is used for collecting described generator daughter nuclide from the generator of selecting described in described a plurality of generators, and wherein said evaporating column comprises suitable post medium; And

Collection container is used for receiving described daughter nuclide from described evaporating column.

2. multigenerator elution system as claimed in claim 1 comprises that further the source of the second eluant, eluent is come from the described daughter nuclide of described evaporating column wash-out.

3. multigenerator elution system as claimed in claim 2, wherein said a plurality of parents-daughter nucleus generator comprises a plurality of Mo99/Tc99m generators ([99Mo] molybdic acid titanium) generator.

4. multigenerator elution system as claimed in claim 2, wherein said a plurality of parents-daughter nucleus generator comprises a plurality of Mo99/Tc99m generators ([99Mo] molybdic acid titanium) gel generator.

5. multigenerator elution system as claimed in claim 2, wherein said the first eluate comprises de-ionized water.

6. multigenerator elution system as claimed in claim 2, wherein said the first eluant, eluent comprises high purity water.

7. multigenerator elution system as claimed in claim 2, wherein said the first eluant, eluent comprises water for injection.

8. multigenerator elution system as claimed in claim 1, wherein said evaporating column is that anion column and wherein said post medium comprise aluminium oxide.

9. multigenerator elution system as claimed in claim 2, wherein said the second eluant, eluent comprise the salt of acid.

10. multigenerator elution system as claimed in claim 9, the salt of wherein said acid is salt solusion.

11. multigenerator elution system as claimed in claim 1 further comprises:

Vacuum source is used for extracting eluant, eluent and by described generator the generator eluate is guided towards described evaporating column.

12. multigenerator elution system as claimed in claim 1 further comprises:

Elongated manifold is connected to described a plurality of generator, and described manifold comprises a plurality of valves, and the individual valve in wherein said a plurality of valves becomes selectable fluid to be communicated with corresponding individual generator in described a plurality of generators.

13. multigenerator elution system as claimed in claim 11, further comprise box body, described box body supports described manifold wherein, and described manifold can be disconnected to the source that can be connected to vacuum source, be used for described first eluant, eluent of the described generator of wash-out, source, described collection container and the waste material container that is used for the second eluant, eluent of the described evaporating column of wash-out.

14. multigenerator elution system as claimed in claim 13, wherein said box body and manifold are engaged by the actuating system cooperation, described actuating system engages described valve in order to each described valve optionally is set in order to fluid is guided by described manifold, and described actuating system further provides described vacuum source.

15. multigenerator elution system as claimed in claim 12, further comprise the second post, described the second post comprises suitable medium and removes competing ions, described ion adversely disturbs the described evaporating column that is connected to described manifold, and wherein said collection post is connected to described manifold, and each described post has and becomes the first port that fluid is communicated with and the second port that becomes fluid to be communicated with the second valve with the first valve.

16. multigenerator elution system as claimed in claim 15, wherein said the second post is cation seperation column.

17. multigenerator elution system as claimed in claim 16, wherein said cation seperation column comprises the post medium, is used for removing chloride from the described eluate that the generator of selecting described in the described generator receives.

18. multigenerator elution system as claimed in claim 1, each in wherein said a plurality of generators is the gel generator.

19. multigenerator elution system as claimed in claim 18, each in wherein said a plurality of generators are one in molybdic acid zirconium gel generator and the molybdic acid titanium gel generator.

20. multigenerator elution system as claimed in claim 15, each in wherein said a plurality of generators is the alumina base generator.

21. multigenerator elution system as claimed in claim 1, wherein said demand data is at a plurality of wash-outs of a period of time requirement from described evaporating column.

22. multigenerator elution system as claimed in claim 1, wherein said control system is based on current demand, demand and at present and at the available active best of breed of selecting generator of subsequently demand point, in order to minimize the waste of the daughter nuclide that is produced by described a plurality of generators in the future.

23. multigenerator elution system as claimed in claim 22, wherein said control system are carried out each wash-out of the generator of the described selection of described daughter nuclide from described a plurality of generators automatically.

24. multigenerator elution system as claimed in claim 1, wherein said demand data manually is input to described receiving element.

25. multigenerator elution system as claimed in claim 1, wherein said demand data automatically is input to described receiving element.

26. multigenerator elution system as claimed in claim 1, wherein said daughter isotope is Tc-99m, and the described post medium of described evaporating column is silver-colored post, and the described post medium of described the second post is aluminium oxide.

27. a multigenerator elution system, it comprises:

A plurality of generators;

Control system, be used for following the tracks of each activity of described a plurality of parent-daughter nucleus generator, receive the demand data of the active requirement that produces of indication, described control system is configured to come generator that wash-out selects from described a plurality of generators in order to the desired amount of daughter isotope is provided with the first eluant, eluent;

Receiving element, be used for receiving supply data and demand data, wherein said supply data comprises the information that allows to calculate the available activity in the described generator, and described demand data comprises at least the amount of the daughter nuclide that will produce and produces the timetable of the amount of described daughter nuclide, described receiving element can operate with described control system, and described daughter nuclide satisfies the demand of described demand data representative from the described wash-out of described a plurality of generators so that control system will be ranked;

Concentrated/anion column, be used for collecting described generator daughter nuclide from the generator of selecting described in described a plurality of generators, wherein said evaporating column comprises suitable post medium; And

Collection container is used for receiving described daughter nuclide from described evaporating column,

Wherein said control system is based on current demand, demand and at present and at the available active best of breed of selecting generator of subsequently demand point in the future, in order to minimize the waste of the daughter isotope that the demand data of all inputs is produced by described a plurality of generators.

28. multigenerator elution system as claimed in claim 27 comprises that further the source of the second eluant, eluent is come from the described daughter nuclide of described evaporating column wash-out.

29. multigenerator elution system as claimed in claim 27, further comprise the second post, described the second post comprises suitable medium and removes competing ions, described ion adversely disturbs the described evaporating column that is connected to described manifold, and wherein said collection post is connected to described manifold, and each described post has and becomes the first port that fluid is communicated with and the second port that becomes fluid to be communicated with the second valve with the first valve.

30. multigenerator elution system as claimed in claim 29, wherein said the second post is cation seperation column, and wherein said cation seperation column comprises the post medium, is used for removing chloride from described the first eluate that the generator of selecting described in the described generator receives.

31. multigenerator elution system as claimed in claim 27, wherein said a plurality of parents-daughter nucleus generator comprise one in a plurality of Mo99/Tc99m generators ([99Mo] molybdic acid titanium) generator and Mo99/Tc99m generator ([99Mo] molybdic acid titanium) the gel generator.

32. multigenerator elution system as claimed in claim 27 further comprises:

Be connected to the elongated manifold of described a plurality of generators, described manifold comprises a plurality of valves, and the individual valve in wherein said a plurality of valves becomes selectable fluid to be communicated with corresponding individual generator in described a plurality of generators.

33. multigenerator elution system as claimed in claim 32, further comprise box body, described box body supports described manifold wherein, described manifold can be disconnected to be connected to the source of vacuum source, described the first eluant, eluent, the source of the second eluant, eluent, described collection container and waste material container, wherein said box body and manifold are engaged by the actuating system cooperation, described actuating system engages described valve in order to each described valve optionally is set so that the guiding fluid passes through described manifold, and described actuating system further provides described vacuum source.

34. the method from a plurality of parents-daughter generator wash-out daughter nuclide may further comprise the steps:

The input supply data is to elution system, and described supply data comprises the information that allows to calculate the available activity in the described generator;

The input demand data is to described elution system, and described demand data comprises at least the exit dose of the daughter nuclide that will produce and produces the timetable of the amount of described daughter nuclide;

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

The described daughter nuclide of generator wash-out of from described a plurality of generators, selecting according to described suitable time of eluent table;

In evaporating column from the generator of selecting described in described a plurality of generators each collected described daughter nuclide;

Described daughter nuclide enters collection container from described evaporating column wash-out.

35. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, wherein said calculating and selection step further comprise the broad sense reduction gradient algorithm analysis of the described activity level that carries out described demand data and described a plurality of generators.

36. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, wherein said calculating and select step further to comprise operation from the simulation of the various elution time tables of described a plurality of generators, and the described elution time table that causes the described daughter nuclide waste of minimum when selecting to satisfy described demand data.

37. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, the described step of wherein inputting demand data further comprises the described demand data of input to receiving element, and described receiving element provides described demand data to described control system.

38. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 37, the described step of wherein inputting demand data further comprises the described demand data of artificial input to the step of receiving element, and described receiving element provides described demand data to described control system.

39. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 37, the described step of wherein inputting demand data comprises further that electronically the described demand data of input is to the step of receiving element automatically.

40. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 39, wherein electronically automatically the described demand data of input further comprise the step that receives described demand data from based on network order processing website to the described step of receiving element.

41. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 37, wherein said calculating and selection step are undertaken by control system, and described control system receives described demand data from described receiving element.

42. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, wherein said input supply data step further comprise the step of the time and date that described first wash-out of the calibration data of inputting each generator, date and time that each generator can be used for using, each generator departs from.

43. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, wherein said calculating and select step consider described parent nuclide half life period, described parent nuclide decay equation, described daughter nuclide half life period, described daughter nuclide decay equation, described wash-out output efficiency, from the time expiration of mark, balance equation and each generator of the available wash-out of described parent nuclide decay.

44. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34 further may further comprise the steps:

Show as for available activity in each of described a plurality of generators of the Time Calculation of timetable;

Be in the described demand data of demonstration in the form in the time of timetable; And

Demonstration is from the elution time table curve of the described selection of described calculating and selection step.

45. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 44 further may further comprise the steps:

Manually make the elution time table curve of described selection invalid;

What calculating resulted from described permission step surmounts elution time table curve;

The described elution time table curve that surmounts that shows described permission step; And

Allow the operator to confirm describedly to surmount elution time table curve and manually make the described elution time table curve that surmounts one of in invalid.

46. further comprising, the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 45, wherein said artificial invalidation step select in described a plurality of generators those will be in the step of the time of described timetable wash-out.

47. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, the described step of wherein inputting supply data further are included in the growth activity level of calculating the generator of selecting described in described a plurality of generators after the described elution step.

48. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 34, wherein said calculating and selection step and described elution step are undertaken by control system.

49. the method from a plurality of parents-daughter generator wash-out daughter nuclide as claimed in claim 48, wherein said control system does not have other operator's input to carry out each described elution step according to the elution curve of described selection.

50. the external member of a multigenerator elution system, described external member comprises:

Adaptable manifold comprises many 3 logical/3 position manifold valves, and described valve will will be directed to separating column from the described eluate in a plurality of parents-daughter generator by the control system operation;

The connector of duct conduits and support; And

Filtrator,

In the wherein said duct conduits each can be adapted to be connected to described generator, and to bottle with to the eluant, eluent source or a plurality of source that are used for from described generator wash-out nucleic.

51. external member as claimed in claim 50, wherein make Rule that each described conduit that can connect described generator, bottle and eluant, eluent source or a plurality of sources arrives described manifold valve, so that only the free end of such conduit need to closely cooperate with described suitable parts.

52. external member as claimed in claim 51, wherein said manifold and conduit are assembled under aseptic condition and packed, if so that suitably unpacking in the clean environment, described external member will be kept suitable aseptic level for pharmaceutical operations.

53. one kind is used for management from the computer program of the wash-out of multigenerator elution system, comprises:

Computer usable medium has the computer usable program code of managing the multigenerator elution system, and computer program comprises:

Receive the computer usable program code of supply data of the input of many parents-daughter generator;

Receive the computer usable program code of active demand data from described generator;

Calculate the computer usable program code of the elution time table of described generator based on the described available activity in the described generator and described demand data; And

The computer usable program code of the generator that the actuating system that guides described elution system according to described elution time table is selected from described generator with wash-out.

54. computer program as claimed in claim 53 further comprises at least one the computer program code in the available activity that shows described supply data, demand data, described generator and the elution time table.

55. computer program as claimed in claim 53, the described computer program code that wherein calculates the elution time table further comprise the computer program code of analyzing to be identified for the described suitable time of eluent table of minimum waste be used to the broad sense reduction gradient algorithm of the described activity level that carries out described demand data and described a plurality of generators.

56. computer program as claimed in claim 53, the described computer program code that wherein be used for to calculate the elution time table further comprises: the computer program code that is used for operation from the simulation of the various elution time tables of described a plurality of generators and selects to cause the described elution time table that the daughter nuclide of minimum wastes when satisfy described demand data.

57. computer program as claimed in claim 53, further comprise for allowing the operator by inputting the new invalid computer program code of elution time table that described computer program makes described calculating that is tied to, and the computer program code that is used for calculating based on described new constraint new elution time table.

58. computer program as claimed in claim 53 further comprises be used to storing described supply data, demand data and elution time table for the computer program code of retrieving in the future.

59. a multigenerator elution system comprises the computing machine for the described computer program of enforcement of rights requirement 53.

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