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EP2585211A2 - Dispositif et procédé de production de composés radiochimiques - Google Patents

Dispositif et procédé de production de composés radiochimiques

Info

Publication number
EP2585211A2
EP2585211A2 EP11828159.1A EP11828159A EP2585211A2 EP 2585211 A2 EP2585211 A2 EP 2585211A2 EP 11828159 A EP11828159 A EP 11828159A EP 2585211 A2 EP2585211 A2 EP 2585211A2
Authority
EP
European Patent Office
Prior art keywords
module
reaction vessel
reaction
radiochemical
dosing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP11828159.1A
Other languages
German (de)
English (en)
Inventor
Marco Müller
Steffen Howitz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GeSiM Gesellschaft fur Silizium-Mikrosysteme mbH
ABX Advanced Biochemical Compounds GmbH
Original Assignee
GeSiM Gesellschaft fur Silizium-Mikrosysteme mbH
ABX Advanced Biochemical Compounds GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GeSiM Gesellschaft fur Silizium-Mikrosysteme mbH, ABX Advanced Biochemical Compounds GmbH filed Critical GeSiM Gesellschaft fur Silizium-Mikrosysteme mbH
Publication of EP2585211A2 publication Critical patent/EP2585211A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/005—Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B01J19/004—Multifunctional apparatus for automatic manufacturing of various chemical products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00002—Chemical plants
    • B01J2219/00027—Process aspects
    • B01J2219/00038—Processes in parallel
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00002—Chemical plants
    • B01J2219/00027—Process aspects
    • B01J2219/0004—Processes in series
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
    • B01J2219/00087—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor
    • B01J2219/00094—Jackets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00132—Controlling the temperature using electric heating or cooling elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00139—Controlling the temperature using electromagnetic heating
    • B01J2219/00141—Microwaves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00281—Individual reactor vessels
    • B01J2219/00283—Reactor vessels with top opening
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00331—Details of the reactor vessels
    • B01J2219/00333—Closures attached to the reactor vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00364—Pipettes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00599—Solution-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • B01J2219/00704—Processes involving means for analysing and characterising the products integrated with the reactor apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00731—Saccharides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00788—Three-dimensional assemblies, i.e. the reactor comprising a form other than a stack of plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00801—Means to assemble
    • B01J2219/0081—Plurality of modules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00873—Heat exchange
    • B01J2219/00882—Electromagnetic heating
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00889—Mixing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00905—Separation
    • B01J2219/00916—Separation by chromatography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00925—Irradiation
    • B01J2219/00934—Electromagnetic waves
    • B01J2219/00941—Microwaves
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

Definitions

  • the invention relates to a device for producing radiochemical compounds, in particular radiochemical medicaments, to a method for producing the radiochemical compounds, to a use of the device and to a kit which can be used in the device.
  • radiolabeled compounds so-called radiotracers
  • these radiotracers can be used to quantify metabolic processes and to record the bio-distribution of the radiodiagnostic from the outside.
  • PET positron emission tomography
  • radiotracers which can be used for positron emission tomography, due to the pharmacokinetics only a few radionuclides into consideration.
  • carbon 11 with a half-life of 20 min and fluorine-18 with a half-life of 110 min has hitherto been preferred.
  • These radioactive nuclides are produced by means of a particle accelerator (cyclotron), which generates the desired radioactive nuclides by bombarding protons or deuterons on specially developed targets.
  • the target for the production of [ 18 F] fluoride is 18 0-enriched water (H 2 18 0, ⁇ -18-water), which has a relatively high price due to its rather complicated distillative production from natural water.
  • the [ 18 F] fluoride produced in the cyclotron is separated from the target water by ion exchange, whereby on the one hand losses of ⁇ -18-water occur and on the other hand the water can be contaminated by contact with the ion exchanger with organic substances.
  • ion exchange ion exchanger
  • acetonitrile reacted (label). All chemical-physical Processes take place in synthesis modules, which, due to a large number of reaction steps (eg ion exchange, distillation, drying, reaction) are equipped with relatively complex control systems.
  • WO 03/078358 A2 discloses a miniaturized device for producing radiolabelled compounds.
  • the device has a reaction chip with an area of 1 cm 2 and has inlet openings for the supply of reactants and outlet openings for discharging the reaction mixture or its components.
  • a further connection can be provided for introducing, for example, a deprotection means.
  • the inlet ports, outlet ports, and other ports are interconnected via a system of microchannels formed in the device.
  • An analysis chip can be connected to the reaction chip, which has two additional connections for the supply or removal of electrolyte buffer solutions in addition to an inlet opening, which is in connection with the outlet opening of the reaction chip, and an outlet opening. From the analysis chip, the reaction mixture finally passes into a separating device in which the desired radiotracer is then obtained.
  • the individual chips can also be realized in a single device, wherein a plurality of microchannels is provided in the individual device.
  • US 2005/0232387 A1 discloses a system for synthesizing a radiochemical compound in a microfluidic environment.
  • the system comprises a microreactor having a plurality of inlet ports, an outlet port, and a microchannel connecting the inlet ports and the outlet port. Via the inlet openings, the precursor and a solution containing the radioactive isotope are supplied. The two substances come into contact with one another in the microchannel, so that during the passage of the two substances through the microchannel, both substances react with one another to obtain the radiochemical compound. At the outlet then the radiochemical compound leaves the microreactor.
  • the reaction in micro-channels is associated with a variety of difficulties.
  • the microfluidics in the channels requires a careful coordination of the fluidics of the components, which usually can only be accomplished with a high outlay on the periphery (eg pumps, valves, heating and cooling units). It becomes even more complicated when different microreactors have to be used for different radiotracers.
  • the cleaning of the microchannels is associated with a high cost. This prevents various radiotracers from being made within a short time with the same microchip.
  • the number of reaction stages that can be performed in the known microreactors is limited. Each stage requires at least one inlet that requires a microchannel that communicates with the channel in which the precursor flows. In general, other outlets are required to remove the waste products.
  • the object of the invention is to eliminate the disadvantages of the prior art.
  • a device for producing radiochemical compounds in particular radiochemical medicaments such as radiotracers, is proposed. ben, which avoids the long reaction times and elaborate purification procedures required in conventional synthesis equipment, and offers high radiochemical yields and high flexibility in the production of different radiotracers.
  • a method for producing radiochemical compounds by means of the device and uses of the device are to be specified.
  • an apparatus for producing radiochemical compounds which comprises at least one reaction module, a dosing module, and a storage module, wherein
  • the reaction module has at least one reaction vessel with a closable opening, through which the substances required for the preparation of a given radiochemical compound, are introduced into the reaction vessel, and over which the prepared radiochemical compound is removed from the reaction vessel;
  • the dosing module has at least one pipetting head, which is movable relative to the supply module and the reaction module and in the x, y and z directions and has at least one dosing unit, and
  • the storage module at least one reservoir for one of the substances that are required for the preparation of the respective radiochemical compound is formed.
  • a washing station for the dosage units is also provided.
  • the device is preferably controlled by means of a control unit, which is expediently formed in the dosing module and can be controlled by software.
  • the device may comprise a purification module for separating the prepared radiochemical compound from the reaction mixture.
  • the cleaning module can include cartridges customary in radiochemistry, in particular chromatographic columns, and / or other cleaning agents, for example high performance liquid chromatography (HPLC).
  • HPLC high performance liquid chromatography
  • the cartridges and / or other cleaning agents required to separate the prepared radiochemical compound from the reaction mixture can also be integrated into the storage module.
  • the device may comprise a dispensing module in which the radiochemical compound purified in the cleaning module is mixed with an aqueous solution for injection, e.g. B. isotonic sodium chloride solution is added to obtain ready-to-use preparations.
  • the dispensing module may comprise a plurality of vials into which the purified radiochemical compound may be filled at a predetermined dose.
  • each of the reaction vessels of the reaction module has an internal volume of from 1 ⁇ to 20,000 ⁇ , more preferably from 1 ⁇ to 5,000 ⁇ , even more preferably from 1 ⁇ to 2,500 ⁇ , and most preferably from 1,000 ⁇ to 2,000 ⁇ .
  • the reaction vessel may be a vial.
  • Each reaction module has at least one reaction vessel, preferably 1 to 50 reaction vessels, more preferably 1 to 10 reaction vessels.
  • Each reaction vessel has an opening through which the substances necessary for the preparation of the respective radiochemical compound can be introduced into the reaction vessel and from which the prepared radiochemical compound can be removed from the reaction vessel. Moreover, gases can also be introduced and / or discharged via the opening. Finally, the opening can also be used to produce overpressure or vacuum (vacuum) in the reaction vessel.
  • radiochemical compounds can be prepared in parallel with only one device according to the invention. Even if only one reaction module is provided, it is possible to switch quickly from the production of a radiochemical compound to the production of another radiochemical compound. This requires only replacement or purification of the reaction vessel (or reaction vessels) and the dosage units. Furthermore, in contrast to the prior art, difficult-to-access radiochemical compounds can also be synthesized rapidly since only the selection of another flowchart in the control unit has to be called up and executed. This is due to the fact that it is only necessary to install additional reaction vessels and / or cleaning modules. This is particularly advantageous in radiochemical compounds that can only be obtained via multi-step reactions.
  • the prior art synthesizers are virtually limited to two stages and require elaborate designs when more than three stages are required.
  • the device according to the invention is for this for example, particularly suitable for the nucleophilic preparation of 18 F-DOPA (6- [ 18 F] fluoro-L-3,4-dihydroxyphenylalanine), which is known to require a three-step reaction.
  • a reaction module preferably comprises a plurality of reaction vessels when the preparation of a given radiochemical compound requires a multi-step process.
  • Several reaction modules are preferably provided when different radiochemical compounds are to be prepared in succession or in parallel by means of the device according to the invention.
  • the device according to the invention avoids the difficulties associated with the microfluidics of known miniaturized synthesis devices for radiochemical compounds. This is due in particular to the flexible control of the pipetting heads in the uptake and release of educts and solvents, while the uptake and release of starting materials and solvents in micro fluidic systems always depends strictly linearly on a flow chart.
  • the device according to the invention is dimensioned such that it can be used in a "standard hot cell.”
  • a “standard hot cell” is understood to mean a space which is delimited against its surroundings by means of shielding walls.
  • the shielding walls are typically made of a material that is impermeable to gamma radiation, for example lead plates.
  • the device can be used in a hot cell whose interior has dimensions of 1 mx lm x Im or less.
  • a further advantage of the device according to the invention is that the preparation of one or more radiochemical compounds can be carried out without the intervention of an operator.
  • substances required for the production of a given radiochemical compound are combined in kits.
  • Each kit can be a supply module of the device according to the invention.
  • the necessary for the preparation of a given radiochemical compound are preferably not provided in the kits but in a separate storage module.
  • kits can be prefabricated so that the device according to the invention only has to be equipped with the kits in order to produce the prescribed radiochemical compound.
  • the assembly of the device according to the invention with the components of a kit can be made on the basis of assembly plans, different assembly plans are provided for different radiochemical compounds, for example assembly plan 1 for a first tracer, tracer A, assembly plan 2 for a second tracer, tracer B, assembly plan for a third tracer, tracer C, etc.
  • the assembly plan is communicated to the user of the device according to the invention together with the kit.
  • the kit may also comprise a carrier plate, for example a microtiter plate.
  • the support plate has reservoirs in which the substances are located. It is then only necessary to position the carrier plate at a predetermined location of the storage module.
  • the support plate is also referred to as a kit plate.
  • the kits can be disposable kits.
  • the kit may contain, in addition to substances required for the preparation of a given radiochemical compound, also the cartridges and / or other required cleaning elements required for the separation of the prepared radiochemical compound from the reaction mixture. The user can insert these cartridges and / or cleaning elements into the cleaning module.
  • the assembly of the cleaning module with the cartridges and / or cleaning elements can then be carried out according to the specifications of the assembly plan, ie the assembly plan includes not only the places where the required substances are positioned in the storage module, but also the places where the cartridges and / or cleaning elements are positioned in the cleaning module.
  • the supply module and the cleaning module of the device according to the invention are thus integrated into the kit. If the user of the device according to the invention wants to produce a specific radiochemical compound, for example Tracer A, one or more kits are made available to him containing the required substances and the cartridges and / or cleaning agents required for this purpose. The user then populates the device according to the invention with the kit on the required substances, cartridges and, if provided, further cleaning agents are provided.
  • the preparation of several radiochemical compounds can be carried out in parallel and / or in succession. If the production of several radiochemical compounds take place in parallel, several reaction modules are required.
  • the reaction module preferably has a heating and / or cooling device.
  • the heating and / or cooling device is expediently arranged below the bottom of the reaction vessel or forms a jacket around the reaction vessel. It is also possible to use a microwave to heat up the reaction vessel.
  • the reaction vessel preferably has a closure, wherein the opening of the reaction vessel is opened when a substance which is required for the preparation of the respective radiochemical compound is introduced into the reaction vessel or the reaction mixture or a part thereof is removed from the reaction vessel. leads, and the opening is closed by means of the closure after completion of the supply or discharge of the substance.
  • the reaction vessel is usually closed and the dosing module is available for further tasks during this time.
  • the closure of an opening of a reaction vessel is preferably gas-tight.
  • the opening can conveniently be opened and closed automatically. This too can be done via the control unit.
  • the reaction vessel is mounted in the reaction module so that it can be vibrated by means of a dosage unit which is introduced into the reaction vessel. In this way, thorough mixing of the reaction mixture in the reaction vessel can be achieved.
  • the reaction vessel may be mounted on a movable support member, so that the reaction vessel can be set in a shaking motion.
  • the carrier element is formed in the reaction module and may contain the heating and / or cooling device.
  • an ultrasonic mixer or a magnetic stirrer can be arranged in the reaction module. Each pipetting head is movable relative to the supply module and the reaction module, wherein storage and reaction modules are suitably fixed.
  • Each pipetting head of the dosing module is movable in the x, y and z directions.
  • the movement of the pipetting head is controlled by a control module, which is expediently arranged in the dosing module and can be controlled by software.
  • the software can be used to specify when the pipetting head performs which movement.
  • the software determines which volumes of the substances required for the production of the radiochemical compound are taken up and delivered by the dosage units of the respective pipette head. If the dosing module has two pipetting heads, then these pipetting heads are preferably movable independently of one another.
  • the advantage of two pipetting heads is that a substance which has been passed through the cleaning module, with a dosage unit, which carries the second pipetting head, can be directly absorbed and processed, whereby an additional reservoir is spared.
  • a dosage unit is understood here to mean a device which has an internal volume into which a predetermined amount of a required substance or of the reaction mixture can be taken up, in which the absorbed amount of the required substance or of the reaction mixture can be transported, and from which the excluded quantity of required substance or the reaction mixture can be delivered.
  • the uptake and release of the substance or of the reaction mixture from the dosage unit is controlled by the control unit.
  • valves or actuators may be provided on the dosage unit, which can be controlled by means of motors, pumps, vacuum or a compressed gas such as compressed air.
  • the necessary means for controlling the valves and actuators may be part of the dosage unit.
  • a dosage unit preferably has a dosing tip. As dosing tip active tips, z.
  • piezoelectrically operated microspheres for dosing pico to nanoliter quanta or passive steel or polymer tips for dosing micro-milliliter quanta can be used.
  • Dosing units for liquids with active and passive dosing tip allow the reproducible and repetitive addressing of single quanta with a volume of 20 picoliters ⁇ 10%, with no upper limits.
  • a metering unit may comprise a fluidically closed circuit of at least one reservoir for system fluids such as deionized water, at least one pump, at least one valve and at least one metering tip.
  • the pump and the valve may be commonly connected to a system as with syringe pumps. Alternatively, however, other pump-valve Arrangements may be provided.
  • the fluidically closed circuit can be realized by means of lines, for example by means of a hose.
  • a dosing module may have different dosage units, in particular dosing units with different structure, which are adapted to the given transport task.
  • Dosing units with dosing tips can be used for receiving, transporting and dispensing liquids.
  • the inclusion of the predetermined amount of the required substance or the reaction mixture in the internal volume, the closure of the amount in the internal volume for transport, and the delivery of the amount of the internal volume are controlled by syringe pumps.
  • the pipetting head can carry a dosing unit, which can remove a powdery substance from the supply module, transport it to the reaction module and introduce it via the opening into a reaction vessel of the reaction module.
  • the pipetting head carries a dosage unit, which removes a pulverulent substance from the storage module, transports it to the reaction module and introduces it via the opening into a reaction vessel of the reaction module, and at least one further dosage unit which consists of the Supply module remove a liquid substance, transport to the reaction module and can introduce tion module via the opening in a reaction vessel of the reaction.
  • the dosing unit which can remove a liquid substance from the storage module, transport it to the reaction module and introduce it via the opening into a reaction vessel of the reaction module can also be used to receive from the reaction vessel the reaction mixture or a part thereof, to transport and to a given place.
  • liquid or “liquid substance” is also intended here to include solutions and dispersions of substances in a solvent. He should also include the reaction mixture.
  • a metering unit should have a first channel for supplying a gas such as nitrogen into the reaction vessel and a second channel for removing gaseous reaction products from the reaction vessel.
  • the first channel can simultaneously serve for receiving, transporting and delivering a required substance or the reaction mixture or a part thereof.
  • the first channel is designed so that it penetrates deeper into the reaction vessel than the second channel. Dosage units are referred to the number of channels as single-lumen, educatelumige, dreilumige, etc. dosage units.
  • a three-lumen dosage unit may include a first channel for receiving, transporting, and delivering a substance needed for the synthesis of the radiochemical compound, a second channel for delivering a gas to a reaction vessel, and a third channel for removing gaseous reaction products from the reaction vessel exhibit.
  • a vacuum may be applied to the third channel.
  • the dosage units By means of the dosage units, liquids and solids can be precisely metered.
  • the dosage units preferably have an internal volume of 10 to 5000 ⁇ , more preferably 50 to 1000 ⁇ .
  • the device according to the invention allows the use of solids for the preparation of predetermined radiochemical compounds, in other words, the required substances can be present as solids.
  • This relates in particular to precursor compounds and catalysts.
  • Solids are preferably used when prolonged storage for malfunction, eg. B. leads to decomposition of the substance.
  • the solids dosage according to the invention allows the dosage of a few ⁇ g mass quanta.
  • metering units adapted to this purpose are provided, which are also referred to hereinafter as solids pipettes. be referred to.
  • the advantage of a solid pipette is the combination of relatively exact dosage and above all easier storage of the substance in a stable dry state.
  • the supply module of a kit with a stock of solids is fundamentally different from a supply of liquids.
  • the solids may be added to a solvent in the dosage unit immediately prior to their use if the substances need to be in solution for the preparation of the radiochemical compound.
  • the use of solids in the dosage units and kits avoids problems due to the inadequate stability of solutions of these solids. This increases the durability of the kits.
  • the device according to the invention enables the use of pulverulent catalysts. This significantly increases the number of radiochemical compounds which can be prepared by means of the device according to the invention.
  • a dosage unit may be provided which can apply liquids to one end of a cleaning cartridge, push through the cleaning cartridge, and resume at the other end of the cleaning cartridge.
  • such a dosing unit has a first channel with an opening which can be brought into contact with the inlet of the cleaning cartridge, so that a liquid can be introduced from the first channel into the cleaning cartridge.
  • the dosage unit further includes a second channel having an opening in contact with the exit of the cleaning cartridge when the opening of the first channel is in contact with the entrance of the cleaning cartridge.
  • one or more storage modules are stored in a microplate stacker. This is particularly advantageous if the storage modules are each in the form of kits comprising kit plates.
  • the microplate stacker may have means for controlling temperature and / or humidity and / or C0 2 concentration.
  • a stacker is a rack in which several kits are stacked with all substances and cleaning cartridges.
  • the microplate stacker and / or a storage module have a transport device, eg. As a gripper or a conveyor belt, which removes the necessary for the preparation of a given radiochemical connection kit from the frame and turns off at a predetermined location within the device according to the invention. Thereafter, the dosing units have access to the substances of the kit.
  • Each kit suitably the kit plate, can have an individual address, which is realized, for example, in the form of a transponder chip or a bar code, whereby a confusion of kits can be ruled out.
  • kits for the synthesis of different or the same radiochemical substances, which can represent a considerable time saving. Any movement of the kit plate from the stacker to the synthesis station and back is via the control unit of the same.
  • the dosage units transport the predetermined amounts of the required substances at a given time from the reservoirs of the storage module into the reaction vessel. If a plurality of metering units are provided, it is also predetermined which of the metering units receives what required substance at which time and transfers it to the reaction vessel.
  • the specifications are stored by means of software in the control unit, which then controls the pipetting head via the robotics.
  • a dosage unit can be used to increase the reactivity or to remove a part of it from the reaction vessel and to transport to a predetermined location, for example, the inlet of the cleaning module, for example an HPLC.
  • the reaction mixture is usually removed from the reaction vessel after reaction of the required substances and contains the desired radiochemical compound, which is then purified in the cleaning module. After completion of the cleaning, the purified radiochemical compound can be transferred to a filling cell.
  • the filling cell is preferably a component of the device according to the invention.
  • radiochemical compound is intended to include all organic or inorganic compounds which have a radioisotope,
  • radiochemical compound includes radiochemicals and diagnostics, more preferably radiotracers, radiopharmaceuticals and radioligands.
  • Preferred radioisotopes are 68 Ga, 90 Y, 99 Tc, 11 64 Cu, Lu 177 , n C, 18 F, 124 I, 13 N and
  • Preferred 18 F-labeled radiotracer are 2-deoxy-2- [ 18 F] fluoro-D-glucose ([ 18 F] - FDG), 6- [ 18 F] fluoro-L-3,4-dihydroxyphenylalanine ([ 18 F ] -FDOPA), 6- [ 18 F] fluoro-L-meta-tyrosine ([ 18 F] -FMT), [ 18 F] fluorocholine, [ 18 F] fluoroethylcholine, 9- [4- [ 18 F] fluoro 3- (hydroxymethyl) butyl] guanine ([ 18 F] FHBG), 9 - [(3- [ 18 F] fluoro-1-hydroxy-2-propoxy) methyl] guanine ([ 18 F] -FHPG), 3- (2 '- [ 18 F] fluoroethyl) spiperone ([ 18 F] -FESP), 3 * -deoxy-3 * - [ 18 F] fluorothymidine (
  • a method for producing radiochemical compounds is further provided by means of the device according to the invention, wherein by means of dosage units, the substances required for the preparation of the respective radiochemical compound are introduced into a reaction vessel of the reaction module and wherein the dosage units via a pipetting head in the x-, y-direction or in the x-, y- and z-direction are movable.
  • substances required for the preparation of the respective radiochemical compound are introduced successively into the reaction vessel of the reaction module.
  • a plurality of dosage units can be used, wherein the same dosage unit can be used for the introduction of multiple substances.
  • the dosage unit should be rinsed after the introduction of a first substance and the inclusion of a second substance in a washing station.
  • the produced radiochemical compound can advantageously also be removed from the reaction vessel by means of a dosage unit.
  • This dosage unit may be one of the dosage units already used for the introduction of a substance into the reaction vessel. Preferably, this dosage unit was previously rinsed in the wash station. After removal from the reaction vessel, the radiochemical compound produced can be transferred by means of the dosing unit to a purification module.
  • the method according to the invention comprises the following steps:
  • step (a) the solution of the radioactive isotope is expediently an aqueous solution.
  • the precursor compound is preferably introduced into the reaction vessel as a solid or dissolved in an organic solvent.
  • the precursor compound can be mixed with an organic solvent immediately before it is introduced into the reaction vessel or can already be provided in dissolved form. If a kit with a kit plate is used, the solution may already be present in the kit, or a solvent may be transferred by means of a dosing unit into the solid material vial on the kit plate in which the undissolved precursor compound is present.
  • the device according to the invention is particularly suitable for the production of radiotracers, radiopharmaceuticals and radioligands.
  • Precursor compounds are also referred to as precursors.
  • precursor compound or “precursor” includes organic or inorganic compounds that react with a radioisotope to yield a radiochemical compound. Examples of precursor compounds are amino acids, nucleosides, nucleotides, proteins, sugars and derivatives of these compounds.
  • the precursor compound often contains protecting groups to protect functional groups that are not intended to react with the radioactive isotope.
  • the protecting groups are preferably separated from the reaction product obtained in step (c).
  • the term "radiotracer" in the present invention an artificial, radioactively labeled endogenous or exogenous substance understood after Contribution to the living body participates in the metabolism and allows a variety of studies or facilitated.
  • radioligand in the present invention is understood to mean a radionuclide-labeled substance which can bind as a ligand to a target protein, for example to a receptor.
  • a kit is also provided, the
  • the kit may comprise other ingredients, in particular the ingredients described above in connection with the kit.
  • Fig. 1 is a schematic representation of an embodiment of the device according to the invention
  • Figure 2a is a schematic sectional view of the reaction module and a metering unit with three channels, the pipette tip is inserted into the reaction vessel.
  • Figure 2b is a schematic sectional view of the reaction module and a dosage unit whose pipetting tip is inserted into the reaction vessel.
  • Fig. 2c is a schematic sectional view of the reaction module with closed reactor during a reaction.
  • Fig. 3 is a schematic representation of the embodiment of the device according to the invention shown in Fig. 1, which is a hot cell used.
  • the synthesis device 1 shown schematically in FIG. 1 has a reaction module 2 with two reaction vessels 3. Each reaction vessel 3 is arranged within a housing 4, which is open at the top. In the housing 4, a cooling and / or heating device 5 is arranged (see Fig. 2a). As shown in FIG. 3, the synthesizer 1 may be arranged in a hot cell 24.
  • the reaction vessel 3 is a substantially cylindrical container which has an opening 6 at its top through which substances can be introduced into the reaction vessel 3 and removed from the reaction vessel 3.
  • the opening 6 of the reaction vessel 3 is closed with a closure 7, when no substances are supplied to the reaction vessel 3 or taken from this.
  • the device 1 furthermore has a dosing module 8.
  • the dosing module 8 comprises a pipetting head 9, which by means of a robotics, which part of the dosing module 8, are relatively and channel-selectively movable in the z-axis to the reaction vessel.
  • the pipetting head 9 is movable as a whole in the x, y axes, with the x and y axes in the plane of the paper, while the z axis is perpendicular to the plane of the paper runs.
  • the movement of the pipetting head 9 is controlled by software.
  • the robotics are controlled via a control module (not shown).
  • the pipetting head 9 carries four dosage units 10a, 10b, 10c and 12. Of course, the number of dosage units smaller or larger than four, as long as at least one dosage unit is provided.
  • a dosage unit 10 is a device that can receive, transport and release a substance.
  • the pipetting head 3 carries the following dosage units: three dosing tips 11 and a powder pipette 12. Each of the dosing tips 11 is connected to a syringe pump disposed in the dosing module 8.
  • the powder pipette 12 is connected to a vacuum-compressed air unit disposed in the dosing module 8.
  • At least one of the metering syringes 11 (for example metering syringe 11b of the dosage unit 10b) has two channels for receiving, transporting and delivering a substance which is required for the synthesis of the radiochemical compound and for supplying a gas into the reaction module and a third channel for the removal of gaseous reaction products.
  • vacuum may be applied to the third channel.
  • acetonitrile (ACN) or an Acetnotril solution can be fed, transported and removed via the first channel.
  • nitrogen can be supplied via the second channel.
  • the apparatus 1 further comprises a storage module 13 containing a reservoir 14 for the substances needed for the synthesis of the desired radiochemical compound.
  • a storage container 15 for receiving a powdery substance (for example Mannose triflate as shown in Example 2) and on the other hand a storage module 16 for receiving liquids.
  • the storage module 16 may comprise a plurality of reservoirs 17 for receiving different liquids. The number of reservoirs 17 should be equal to or greater than the number of liquid substances needed for the synthesis of the radiochemical compound.
  • a storage module 16 with six reservoirs 17 is shown.
  • Fig. 1 shows a washing station 18, which may be formed separately from the storage module 13. The washing station has reservoirs 18 which contain cleaning substances for the dosage units 10.
  • Example 2 The mode of operation of the device shown in FIG. 1 is described in the following Example 2 with reference to the production of [ 18 F] -FDG.
  • anhydrous 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-beta-D-mannopyranose also referred to as mannose triflate or TATM
  • TATM mannose triflate
  • Fluorination of the precursor is accomplished by introducing 18 F by nucleophilic substitution to give 2- [ 18 F] fluoro-1,3,4,6-tetra-O-acetyl-D-glucose in acetonitrile under a nitrogen atmosphere.
  • the protecting groups are removed by basic hydrolysis.
  • the basic hydrolysis is typically carried out with sodium hydroxide at temperatures of 80 ° C.
  • citrate buffer solution consisting of: 25.2 mg di-sodium hydrogen citrate-1, 5-hydrate, 144.4 mg trisodium citrate 2-hydrate, 86.9 mg sodium chloride, 2.9 ml water for injections; 0.1 ml hydrochloric acid (2 M), reservoir 14f of storage module 13, (8) 0.9% NaCl solution, reservoir 17c of storage module 16
  • Stock module 13 and stock module 16 are each prefabricated kits. Both kits include a kit plate. Supply module 13 further comprises a QMA cartridge for separating the enriched water from the [ 18 F] fluoride. Stock module 16 includes substances needed in the majority of methods for making radiochemical compounds, while stock module 13 includes the substances needed specifically for the preparation of the given radiochemical compound. The aqueous [ 18 F] fluoride solution is housed in a separate storage module.
  • the dosing module 8 moves the pipetting head 9 with the first dosing syringe 11a to the reservoir 19.
  • l, 2 ml of [ 18 F] fluoride are taken up by the dosing syringe 11a.
  • the pipetting head 9 moves the syringe I Ia, containing the [18 F] fluoride, then to the supply module 13, which is present as a kit, with the QMA cartridge and outputs the [18 F] fluoride on the QMA cartridge.
  • the continuous aqueous solution is taken up with a metering syringe 11c of the dosage unit 10b and discharged again in the storage container 21.
  • the eluent solution from stock module 13 (kit) is taken up with the metering syringe 11a and added to the QMA cartridge.
  • the continuous eluent solution with the [ 18 F] fluoride becomes received by the second metering syringe I Ib of the second dosage unit 10b and filled in the reaction vessel 3.
  • Dosage syringe 1b is a three-lumen dosing syringe with a first inner channel 21 for supplying nitrogen, a second inner channel for the addition of Acetonitrile for azeotropic drying and a third inner channel for vacuum extraction.
  • the channel for vacuum extraction 23 is used to remove the nitrogen supplied and any waste products.
  • the dosing module 8 moves the pipetting head 9 with the powder pipette 12 from its starting position to the powdered substance reservoir 15.
  • the powder pipette 12 receives by means of a vacuum-compressed air unit 20 mg of mannose triflate from the reservoir 15.
  • the pipetting head 9 then moves the powder pipette 12 containing the mannose triflate to an empty vial 22 placed on the storage module 13 (kit).
  • the discharge of the mannose is released by means of the vacuum-compressed air unit. Triflats into the empty vial 22 causes.
  • the metering module 8 moves the pipetting head 9 with the first metering syringe 11a to the second reservoir 14 in the storage module 13.
  • the pipetting head 9 moves the dosing syringe 11a containing the precursor solution to the reaction vessel 3.
  • the closure 7 is removed from the opening 6 of the reaction vessel 3, with the penetrating dossier tip opening 6 hermetically seals.
  • the closure 7 When introducing the metering syringe 1 la in the reaction vessel 3, the closure 7 is removed from the opening 6 of the reaction vessel 3, wherein the penetrating dossier tip closes the opening 6 airtight.
  • the delivery of the precursor solution into the reaction vessel 3 is effected by means of the syringe pump.
  • the temperature of the reaction mixture located in the reaction vessel 3 is raised to 100 ° C.
  • the metering syringe 11a is then removed from the reaction vessel 3, the opening 6 of the reaction vessel being closed by the closure 7.
  • the dosing module 8 then moves the pipetting head 9 with the dosing syringe 1 la to the washing station 18, the dosing syringe 11a being washed with acetone.
  • the dosing 8 moves the pipetting head 9 with the first metering syringe I Ia to the second storage vessel 14 in the storage module 13.
  • the pipetting head 9 then moves the dosing syringe with the ethanol to the reaction vessel 3.
  • the closure 7 is opened from the opening 6 of the reaction vessel 3, wherein the penetrating Dossierspitze closes the opening 6 airtight.
  • the delivery of the ethanol into the reaction vessel 3 is effected by means of the syringe pump.
  • the dosing module 8 moves the pipetting head 9 with the dosing syringe 11a to the washing station 18, the dosing syringe 11a being washed with acetone.
  • the dosing module 8 moves the pipetting head 9 with the first dosing syringe 11a to the second storage vessel 14 in the supply module 13 (kit).
  • the syringe pump 500 ⁇ 2N sodium hydroxide are taken up by the metering syringe I Ia.
  • the pipetting head 9 moves the dosing syringe l la.l containing the sodium hydroxide solution, then the reaction vessel 3.
  • the closure 7 is removed from the opening 6 of the reaction vessel 3, wherein the penetrating Dossierspitze the opening 6 closes airtight.
  • the delivery of the sodium hydroxide solution into the reaction vessel 3 is effected by means of the syringe pump.
  • the temperature of the reaction mixture in the reaction vessel 3 is raised to 80 ° C.
  • the metering syringe 11a is then removed from the reaction vessel 3, the opening 6 of the reaction vessel being closed by the closure 7.
  • the dosing module 8 moves the pipetting head 9 with the dosing syringe 11a to the washing station 18, the dosing syringe 11a being washed with acetone.
  • the dosing module 8 moves the pipetting head 9 with the first dosing syringe 11a to the third supply container in the storage module 13.
  • the pipetting head 9 moves the dosing syringe 11a containing the hydrochloric acid, then to the reaction vessel 3.
  • the dossier tip is introduced into the reaction vessel 3 as soon as the temperature is reached by means of the cooling and heating direction 5 of the reaction mixture located there has reached room temperature.
  • the closure 7 When inserting the metering syringe 1 la into the reaction vessel 3, the closure 7 is removed from the opening 6 of the reaction vessel 3, the penetrating pipetting tip sealing the opening 6 airtight. After the penetration of the pipetting tip of the metering syringe 11a, the delivery of the hydrochloric acid into the reaction vessel 3 is effected by means of the syringe pump. The dosing syringe 11a is then removed from the reaction vessel 3, the opening 6 of the reaction vessel being closed by the closure 7. Then the dosing module 8 moves the pipetting head 9 with the dosing syringe 11a to the washing station 18, the dosing syringe 11a being seen with acetone.
  • the dosing module 8 moves the pipetting head 9 with the first dosing syringe 11a to the reservoir 17a in the reservoir 16.
  • the pipetting head 9 moves the dosing syringe 11a, which contains the water, then to the reaction vessel 3.
  • the dossier tip is introduced into the reaction vessel 3.
  • the closure 7 is removed from the opening 6 of the reaction vessel 3, wherein the penetrating dossier tip closes the opening 6 airtight.
  • the dosing module 8 moves the pipetting head 9 with the dosing syringe 11a for cleaning (cartridge) to the kit 13 and presses the entire aqueous solution with the radiotracer 18F-FDG over the cartridge.
  • the continuous aqueous solution is taken up with a second dossier tip 11c of the dosage unit 10b and transported to the end vial 20 with attached sterile filter.
  • the aqueous solution is filled through the sterile filter into the end vial 20.
  • the end vial 20 already contains a citrate Buffer solution, which was filled during the hydrolysis of Radiotracers of the free Dossierspitze I Ia on the sterile filter.
  • Example 3 corresponds to Example 2, except that an additional step, step 8, is provided for the distribution of patient doses.
  • the isotonic saline solution (0.9%) is removed from the reservoir 17c and distributed to several vials with attached sterile filter, in position 23 on the device 1.
  • the individual patient doses can then be removed from the end vial 20 with the dosing module 8 and distributed to the individual isotonic saline solutions by means of the dossier tip 11a.

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Abstract

Dispositif de production de composés radiochimiques, qui comporte au moins un module de réaction, un module de dosage et un module réservoir, le module de réaction comprenant au moins une cuve de réaction pourvue d'un orifice pouvant être fermé par lequel des substances nécessaires pour la production d'un composé radiochimique prédéfini peuvent être introduites dans la cuve de réaction du module de réaction et par lequel le composé radiochimique produit peut être prélevé de la cuve de réaction du module de réaction. Le module de dosage comporte au moins une tête de pipettage mobile par rapport au module réservoir et au module de réaction dans les directions x, y et z, et au moins une unité de dosage. Dans le module réservoir est conçu au moins un réservoir pour une des substances nécessaires pour la production du composé radiochimique concerné.
EP11828159.1A 2010-06-22 2011-06-20 Dispositif et procédé de production de composés radiochimiques Withdrawn EP2585211A2 (fr)

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DE102010017511A DE102010017511A1 (de) 2010-06-22 2010-06-22 Vorrichtung und Verfahren zur Herstellung radiochemischer Verbindungen
PCT/DE2011/075143 WO2012041305A2 (fr) 2010-06-22 2011-06-20 Dispositif et procédé de production de composés radiochimiques

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CA2803023C (fr) 2018-08-21
US9556081B2 (en) 2017-01-31
US20130144051A1 (en) 2013-06-06
WO2012041305A2 (fr) 2012-04-05
US8980184B2 (en) 2015-03-17
US20150133650A1 (en) 2015-05-14
DE102010017511A1 (de) 2012-02-02
WO2012041305A3 (fr) 2012-10-04
CA2803023A1 (fr) 2012-04-05
US9260354B2 (en) 2016-02-16
US20160115092A1 (en) 2016-04-28

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