EP1820197B1 - Procede et dispositif pour isoler un radionucleide 68ga purifie chimiquement et radiochimiquement, et pour marquer un precurseur de marquage au moyen de ce radionucleide 68ga - Google Patents

Procede et dispositif pour isoler un radionucleide 68ga purifie chimiquement et radiochimiquement, et pour marquer un precurseur de marquage au moyen de ce radionucleide 68ga Download PDF

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EP1820197B1
EP1820197B1 EP05823617A EP05823617A EP1820197B1 EP 1820197 B1 EP1820197 B1 EP 1820197B1 EP 05823617 A EP05823617 A EP 05823617A EP 05823617 A EP05823617 A EP 05823617A EP 1820197 B1 EP1820197 B1 EP 1820197B1
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vessel
labelling
radionuclide
radiopharmaceutical
cation exchanger
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EP1820197A2 (fr
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Frank RÖSCH
Dimitri Vladimirovich Filosofov
Konstantin Zhernosekov
Marc Jennewein
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Johannes Gutenberg Universitaet Mainz
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Johannes Gutenberg Universitaet Mainz
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    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/0005—Isotope delivery systems
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G4/00—Radioactive sources
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G4/00—Radioactive sources
    • G21G4/04—Radioactive sources other than neutron sources
    • G21G4/06—Radioactive sources other than neutron sources characterised by constructional features
    • G21G4/08—Radioactive sources other than neutron sources characterised by constructional features specially adapted for medical application

Definitions

  • the invention relates to a method and apparatus for isolating a 68 Ga radionuclide from a 68 Ge / Ga generator eluate and for labeling a label precursor with the 68 Ga radionuclide to form a radiopharmaceutical.
  • PET positron emission tomography
  • Radionuldidgeneratoren are used, wherein the obtained daughter Radionuldide generally have short half-times T 1 ⁇ 2 in comparison with their parent radionuclides.
  • Such radionuclide generators are based on a concept of effective radiochemical separation of decaying mother and daughter radionuldides in such a way that the daughter void should be obtained in radionuclidically and radiochemically as pure a form as possible.
  • radionuclide generators Compared to in-house radionuclide production facilities such as accelerators or nuclear reactors, the availability of short-lived radionuclides from radionuclide generators offers a cheap and easy alternative.
  • radionuclide generators over the last three decades has always been shaped by the growing spectrum of applications of radionuclides and labeled agents in medicine, particularly for nuclear medicine diagnostics and therapy.
  • promising applications of generator-based therapeutic radionuclides in nuclear medicine, oncology and cardiology have been developed in recent years. This growing importance of radionuclide generators has stimulated a broad development of radionuclide production for radionuclide generators, for adequate radiochemical separations as well as for reliable engineering design of radionuclide generator systems.
  • Radionuclide generator developments have often been systematized. Detailed reports have covered several aspects: parent-daughter half-lives, reactor-produced Nuldides, accelerator-produced Nuldide, generator mother nuclide cyclotron production, ultra-short-lived generator-produced radionuclides, generator-based positron-emitting radionuclides, clinical applications.
  • the initial generator systems separated 68 Ga as an EDTA complex of 68 Ge adsorbed on alumina or zirconia, with the resultant neutral [ 68 Ga] EDTA solution serving to image tumors.
  • 68 Ge was retained on antimony oxide Sb 2 O 5 and 68 Ga was eluted with oxalate solutions.
  • Anion exchange resins and dilute HF solutions as eluent allowed highly effective separations due to the significant Differences in the distribution coefficients of the elements.
  • the breakthrough of 68 Ge was below 10 -4 percent for up to 600 elutions; the 68 Ga yield was greater than 90%.
  • 68 Ge / 68 Ga generators were developed leading to ionic 68 Ga 3+ eluates.
  • 68 Ge was fixed on inorganic matrices such as alumina Al (OH) 3 and Fe (OH) 3 , on SnO 2 , ZrO 2 , TiO 2 or CeO 2 .
  • Tin (IV) oxide SnO 2 showed the best parameters for 68 Ge breakthrough (10 -6 -10 -5 % by bolus) and 68 Ga 3+ elution yield (70-80%) in 1 M HCl.
  • the 68 Ge content defines the radiochemical purity of the separated 68 Ga fraction. Even an initial contamination of about 10 -2 %, corresponding to, for example, 1 ⁇ Ci 68 Ge in a 68 Ga fraction of a 10 mCi 68 Ge / Ga generator system, already seems marginal with regard to a subsequent medical application.
  • 68 Ga eluate volume and chemical purity are further important data for the use of 68 Ga for the synthesis of radiopharmaceuticals.
  • this contamination is also radiochemically relevant, particularly with regard to potential medical applications.
  • the post-elution procedure should therefore explicitly include a chemical strategy for further separation of the 68 Ge.
  • the 68 Ga-labeling of potential radiophannaka plays a central role, for which the corresponding chemical reaction parameters have to be optimized.
  • the trivalent gallium already hydrolyzes above pH> 2 and has a pronounced tendency to adsorb on surfaces of glass and polymers at pH> 3, in particular in the state of low 68 Ga concentrations ( no-carrier-added ), as they result from the generator system results.
  • special reaction conditions have to be chosen because of the complexing kinetics as well as because of the aqua-chemistry of the Ga (III) cation.
  • impurities contained therein may also interfere with high labeling yields, even in the buffer systems typically used in 68 Ga tags.
  • solvent evaporation processes to reduce the volumes of the generator eluates or the final solutions of the 68 Ga radiopharmaceuticals can lead to loss of activity, both by the associated longer process time and by adsorption losses on the vessel walls.
  • This fraction is then added to 10-20 nmol of DOTATOC in a small volume of 1M HEPES or other aqueous buffer solution. Again, potential contamination by the concentrated buffer system can not be excluded.
  • the object of the invention is to provide a method and an apparatus to provide the high purity 68 Ga eluate, which is largely free of chemical and radiochemical impurities, with high yield and very low Eluatvolumen available.
  • the chemical reaction parameters such as the pH of the 68 Ga for the labeling of marker precursors to be optimized.
  • a method for labeling potential radiopharmaceuticals for positron emission tomography is to be provided.
  • This object is achieved in accordance with the invention by a process in which the initial 68 Ge / Ga generator eluate is fed directly to a cation exchanger and 68 Ga is quantitatively adsorbed on the cation exchanger, simultaneously chemically and radiochemically purified and the 68 Ga radionuclide with a marketed precursor from a ligand or a a peptide or protein covalently linked to a ligand is combined to form a radiopharmaceutical.
  • the cation exchanger from the group of strongly acidic cation exchanger polystyrene / divinylbenzene (DVB) resins is selected with a DVB content of 2 to 20%, based on the crosslinked polymers of the resins, and becomes the matrix of the cation exchanger with 68 Ga loaded.
  • the sulfonated polystyrene / divinylbenzene (DVB) resins have a gel-like structure and permanently have negatively charged sulfonic acid groups. Each of these active groups has a fixed electrical charge and is in equilibrium with a number of equivalent oppositely charged ions which are free to exchange with other ions of the same charge.
  • the 68 Ga fraction adsorbed on the cation exchanger is cleaned with acid solutions of the HCl / acetone or HCl / ethanol or analog systems type so that chemical impurities such as Fe (III) and Zn (II) elute from the cation exchanger become.
  • chemical impurities such as Fe (III) and Zn (II) elute from the cation exchanger become.
  • elution 68 Ga remains completely on the cation exchanger, and there is a substantial separation of initially eluted Ti (IV).
  • the chemically and radiochemically pure 68 Ga radionuclide obtained by the elution can be used directly for the synthesis of radiopharmaceuticals.
  • the apparatus for isolating a chemically and radiochemically purified 68 Ga radionuclide from a 68 Ge / Ga generator eluate and for labeling a label precursor with the 68 Ga radionuclide in an embodiment of the invention, includes a conveyor connected by a line to a 68 Ge / Ga generator a number of conveyor means for purifying the 68 Ga fraction adsorbed on a cation exchanger, a synthesis device, into which a line leads from the exit of the cation exchanger, and in which the 68 Ga radionuclide and the labeling precursor are converted into a radiopharmaceutical, and for cleaning the radiopharmaceutical a cartridge, at the input conveyors are connected via lines and their output via a 3rd Way valve is connected to a line leading out of the synthesis device, a storage vessel and a product container for receiving the radiopharmaceutical.
  • the device after Fig. 1 includes a 68 Ge / Ga generator 1, which is preceded by a conveyor 2, for example in the form of a piston, a syringe or a peristaltic pump (peristaltic pump), via a line.
  • the conveyor 2 is connected in a manner not shown with a liquid-filled storage or reservoir, if it is a Schlauchradpumpe. In the case of a piston or a syringe these are filled directly with a liquid.
  • the output of the generator 1 is connected via a first 3-way valve 12 to the cation exchanger 14 on the input side.
  • conveyors 3, 4, 5, 6, 7 are connected via lines to the 3-way valve 12.
  • 68 Ge / Ga radionuclide generators it is preferred, in a manner not shown, several 68 Ge / Ga radionuclide generators simultaneously or sequentially eluted and the common initial eluates transferred to the cation exchanger 14.
  • the 68 Ge / Ga generators can still be operated or used even if their initial 68 Ga eluate already contains an impermissibly high amount of 68 Ge. This significantly extends the useful life of a 68 Ge / Ga generator, especially for generators with 50 or more mCi 68 Ge.
  • the cation exchanger 14 is connected on the output side to a second 3-way valve 15.
  • a line 25 leads from the 3-way valve 15 to a waste container 19
  • a further line 23 leads from the 3-way valve 15 in a marking vessel 21, which is arranged in a synthesis device 20 of the device.
  • the heatable synthesis device 20 is equipped with a heater 22 and is seated on a vertically movable table 27. By lowering the table 27 access to the marking vessel 21 is facilitated.
  • the components of the device described so far are used to isolate the 68 Ga eluate, its volume reduction and purification.
  • a stable plate can accommodate the synthesis device 20, as well as a laterally movable on rails or rollers slide.
  • a line 24 leads from the marking vessel 21 to a third 3-way valve 13.
  • the 3-way valve 13 is connected on the input side to a cartridge 11. From the 3-way valve 13 further leads a line 25 to a storage vessel 18 for the purified Mark istsagens.
  • Another line 26 connects the storage vessel 18 with the product vessel 17. In this line 26, a filter 16 is arranged before entering the product vessel 17. In the product vessel 17, the radiopharmaceutical is provided for administration and may be withdrawn therefrom at any time.
  • the unit of filter 16, product vessel 17, line 26 is used for sterile filtration, which is an independent process step that can be performed in isolation. If necessary, therefore, the unit 16, 17 decoupled from the overall device and operated independently.
  • the operation of the device is based on the flowchart according to FIG. 2 described.
  • the cation exchanger is a strongly acidic cation exchanger from the group polystyrene / divinylbenzene (DVB) resins with a DVB content of 2 to 20%, based on the crosslinked polymers of the resins.
  • the sulfonated polystyrene / divinylbenzene (DVB) resins have a gel-like structure and permanently have negatively charged sulfonic acid groups. Each of these active groups has a fixed electrical charge and is in equilibrium with a number of equivalent oppositely charged ions which are free to exchange with other ions of the same charge.
  • this solution is fed through the 3-way valve 12 to the cation exchanger 14 through the conveyor 5, which is filled with a second acidic solution of HCl / acetone or HCl / ethanol or analog systems, and through this acidic solution 68 Ga eluted from the cation exchanger and introduced via the 3-way valve 15 and line 23 into the marking vessel 21.
  • the remaining residues of Ti (IV) on the cation exchanger 14 are at first rinsed with HCl from the conveyors 6 at the appropriate time and sensed in the waste container 19; Subsequently, the cation exchanger is washed analogously with water from the conveyors 7, whereby the cation exchanger is finally ready for a new procedure.
  • the optimum temperature is equal / higher than 95 ° C.
  • the pH of the label precursor in the labeling vessel 21 is in the range of 2 to 5.
  • a preferred pH is, for example, 2.3.
  • the pH is adjusted by the volume of water and labeling precursor, preferably without a buffer solution, and the supplied HCl / acetone or HCl / ethanol solution or analogous systems.
  • the amount of the label precursor of a ligand or ligand covalently linked to a peptide or protein, such as DOTATOC, in the labeling vessel 21 is about 1 to 100 nmol, preferably 7 to 14 nmol, plus an appropriate volume of water or buffer or HEPES or analogous systems to adjust the pH.
  • the liquid-containing conveyor 8 is operated with open 3-way valve 13 so that via the line 24 from the marker vessel 21, the radiopharmaceutical is applied to the cartridge 11 and is fixed. Thereafter, the 3-way valve 13 closes the line 24 and opens the line 25, which leads into the storage vessel 18 - or optionally in another, not shown storage vessel.
  • the cartridge 11 is washed with pure water or analogous solvents which elute free 68 Ga or other unlabeled 68 Ga species, and removed in a manner not shown, for example, back into the now no longer required 21 Mark istsgefpiping.
  • the conveyor 10 containing less than 0.5 ml of ethanol or analogous solvents, the elution of the radiopharmaceutical, for example 68 Ga-DOTATOC, from the cartridge 11 and its introduction into the storage vessel 18 containing an isotonic saline solution , Alternatively, the specified fraction can also be eluted into an empty storage vessel 18, which in principle allows the removal of the ethanol or analogous solvent.
  • the radiopharmaceutical for example 68 Ga-DOTATOC
  • the 3-way valve 13 closes the line 25 and by means of a device, not shown, the radiopharmaceutical is drawn through the conduit 26 from the storage vessel 18 and introduced via a filter 16 into the product vessel 17.
  • a filter 16 is a sterile filtering, so that thereafter the radiopharmaceutical is ready for use.
  • the binding of the 68 Ga to the labeling precursor is more than 75%, based on the decay-corrected activity of the initial 68 Ge / Ga generator eluate.
  • the reactivity of the label precursor at 10 mCi of the 68 Ge / Ga generator elute is up to 80%, 90% and more than 95% after one, five and ten minutes.
  • the duration of the procedure from application of the initial generator eluate to the provision of the radiopharmaceutical is about 20 minutes.
  • the conveyors 2 to 10 and the lines connected to them can be subjected to negative pressure in order to transport the solutions through the lines.
  • the octapeptide octreotide has a high affinity for the sstr2 subtype of human somatostatin receptor-expressing tumors, and the conjugated macrocyclic bifunctional chelator DOTA coordinately binds the trivalent 68 Ga 3+ with high thermodynamic and kinetic stability also in vivo.
  • this type of 68 Ga-labeled compounds allows excellent visualization of tumors and small metastases.
  • This 68 Ga tumor targeting approach may potentially be extended to a variety of other tumors, using other peptides.
  • 68 Ga also finds applications in myocardial perfusion diagnostics in the form of the [ 68 Ga] BAT-TECH complex as a perfusion tracer. This shows that, in principle, any type of 68 Ga labeling via ligand structures can be used for nuclear medical diagnostics altogether or will be in the future.
  • the "kit” -like synthesis offers another advantage, as does the use of PET independent of in-house direct production from established positron emitters such as 18F .
  • the device is also suitable for concentrating and purifying radiogallium solutions. It is also suitable for cleaning, volume reduction of gallium radioisotopes and labeling of marrow precursors with the 66 Ga or 67 Ga radioisotope.
  • the device is equally well suited for labeling ligands or ligand-covalently linked peptide or protein with radionuclides other than 68 Ga.
  • radionuclides other than 68 Ga.
  • An example of this is 90 Y, which requires purification of the eluate from other metals.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Claims (29)

  1. Procédé pour obtenir un radionucléide 68Ga à partir d'un éluat générateur de 68Ge/Ga, qui contient le radionucléide 68Ga sous forme ionique, dans lequel l'éluat initial générateur de 68Ge/Ga est acheminé directement à un échangeur et le 68Ga est adsorbé quantitativement sur l'échangeur et, en même temps, chimiquement et radiochimiquement purifié et le radionucléide 68Ga est combiné avec un précurseur de marquage constitué d'un ligand pour donner un produit radiopharmaceutique, caractérisé en ce que l'on choisit, comme échangeur, un échangeur cationique choisi dans le groupe des échangeurs cationiques fortement acides, tels que des résines de polystyrène/divinylbenzène (DVB), avec une fraction de DVB de 2 à plus de 20 %, par rapport aux polymères réticulés des résines, et la matrice de l'échangeur cationique est chargé de 68Ga.
  2. Procédé selon la revendication 1, caractérisé en ce que le radionucléide 68Ga est combiné avec un précurseur de marquage constitué d'un peptide ou d'une protéine lié(e) par covalence à un ligand pour donner un produit radiopharmaceutique.
  3. Procédé selon la revendication 1, caractérisé en ce que plusieurs générateurs de radionucléides 68Ge/Ga sont élués simultanément ou consécutivement et les éluats initiaux communs sont transférés sur l'échangeur cationique.
  4. Procédé selon la revendication 1, caractérisé en ce que le 68Ge initialement élué n'est pas adsorbé et une purification chimique du 68Ga a lieu sur l'échangeur cationique, au cours de laquelle la contamination de 68Ge radiochimique est réduite jusqu'à une valeur inférieure à 10-8 pour cent.
  5. Procédé selon la revendication 3, caractérisé en ce que des générateurs de 68Ge/Ga peuvent encore opérer si leur éluat de 68Ga initial contient déjà 50 mCi ou plus de 68Ge.
  6. Procédé selon la revendication 4, caractérisé en ce que l'on procède à une purification avec des solutions acides du type HCl/acétone ou HCl/éthanol ou des systèmes analogues de manière à éluer des impuretés chimiques, telles que Fe(III) et Zn(II), de l'échangeur cationique.
  7. Procédé selon la revendication 4, caractérisé en ce qu'il se produit une ample séparation du Ti(IV) initialement élué au cours des processus d'élution de 68Ga.
  8. Procédé selon la revendication 1, caractérisé en ce que le radionucléide 68Ga purifié et réduit en volume est élué directement dans un récipient de marquage, dans lequel sont introduits le précurseur de marquage et de l'eau pure ou des systèmes tampons.
  9. Procédé selon la revendication 1, caractérisé en ce que le radionucléide 68Ga purifié et réduit en volume est élué directement dans un récipient, à partir duquel peuvent se faire des remplissages de ballons.
  10. Procédé selon la revendication 1, caractérisé en ce que le précurseur de marquage contient un ligand choisi dans le groupe des chélatants de stabilité thermodynamique et cinétique appropriée pour la formation des complexes correspondants de type Ga-ligand, tels que DTPA, DOTA, NOTA, DFO, etc., ainsi que de leurs dérivés.
  11. Procédé selon la revendication 10, caractérisé en ce que l'on choisit les complexes de Ga-ligand dans le groupe constitué du DTPA, du DOTA, du NOTA, du DFO, etc., ainsi que de leurs dérivés.
  12. Procédé selon la revendication 8, caractérisé en ce que le précurseur de marquage constitué d'un ligand ou d'un peptide ou d'une protéine lié(e) par covalence à un ligand ou d'autres composés est introduit dans le récipient de marquage en quantité d'environ 1 à 100 nmoles, en particulier de 7 à 14 nmoles.
  13. Procédé selon les revendications 8 à 10, caractérisé en ce que la liaison du 68Ga sur le précurseur de marquage est supérieure à 75 %, par rapport à l'activité - corrigée au plan décomposition - de l'éluat initial générateur de 68Ge/Ga.
  14. Procédé selon la revendication 8, caractérisé en ce que le produit radiopharmaceutique est transféré du récipient de marquage à une cartouche, sur laquelle est fixé le produit radiopharmaceutique, et en ce que le 68Ga libre et/ou d'autres espèces de 68Ga est ou sont élué(s) sur la cartouche.
  15. Procédé selon la revendication 14, caractérisé en ce que la cartouche est lavée avec un liquide, en particulier de l'eau ou des systèmes analogues, et purifiée du 68Ga libre et/ou d'autres espèces de 68Ga.
  16. Procédé selon la revendication 14, caractérisé en ce que le produit radiopharmaceutique est élué avec moins de 0,5 ml d'éthanol ou de systèmes analogues.
  17. Procédé selon la revendication 14, caractérisé en ce que le produit radiopharmaceutique est élué de la cartouche dans un récipient vide pour d'autres traitements individuels ou dans un récipient avec un volume correspondant de solution isotonique de sel de cuisine, à partir duquel il subit une filtration stérile et en ce qu'il est mis à la disposition pour application.
  18. Procédé selon la revendication 8, caractérisé en ce que l'on ajuste la valeur de pH des solutions destinées à la synthèse du produit radiopharmaceutique dans le récipient de marquage à une valeur de 2,0 à 5,0, en particulier de 2,3, et l'on n'utilise que de l'eau ou bien des systèmes tampons ou des solutions HEPES et similaires.
  19. Dispositif pour isoler un radionucléide 68Ga chimiquement et radiochimiquement purifié d'un éluat générateur de 68Ge/Ga, contenant un dispositif de transport (2) raccordé par une conduite à un générateur de 68Ge/Ga (1), un dispositif de synthèse (20), auquel mène une conduite (23) depuis la sortie de l'échangeur (14) et dans lequel le radionucléide 68Ga est transformé en produit radiopharmaceutique, une soupape à 3 voies (13), qui est raccordée au dispositif de synthèse (20) par une conduite (24) et qui ressort du dispositif de synthèse (20), un récipient de réserve (18) et un récipient de produit (17), caractérisé en ce que l'échangeur est un échangeur cationique (14) et est raccordé à un certain nombre de dispositifs de transport (3, 4, 5, 6, 7) pour purifier la fraction de 68Ga adsorbée sur l'échangeur cationique (14), en ce que un précurseur de marquage est marqué par un radionucléide 68Ga, 66Ga ou 67Ga dans le dispositif de synthèse (20) et transformé en produit radiopharmaceutique, et en ce qu'il y a une cartouche (11) pour la purification du produit radiopharmaceutique, à l'entrée de laquelle des dispositifs de transport (8, 9, 10) sont raccordés par des conduites et la sortie de laquelle est raccordée, via la soupape à 3 voies (13), à la conduite (24) qui ressort du dispositif de synthèse (20).
  20. Dispositif selon la revendication 19, caractérisé en ce que les dispositifs de transport (2 à 10) sont des pistons, des injecteurs ou des pompes péristaltiques à effet bidirectionnel.
  21. Dispositif selon la revendication 19, caractérisé en ce que le transport se fait par les dispositifs de transport (2 à 10) au moyen d'une dépression.
  22. Dispositif selon la revendication 19, caractérisé en ce que le dispositif de synthèse (20) contient un récipient de marquage (21), dans lequel avance la conduite (23), qui est raccordée à une soupape à 3 voies (15), elle-même raccordée à la sortie de l'échangeur cationique (14) et à une conduite pour parvenir à un récipient de déchets (19).
  23. Dispositif selon la revendication 19, caractérisé en ce qu'une conduite (25) mène depuis la soupape à 3 voies (13) au récipient de réserve (18).
  24. Dispositif selon la revendication 19, caractérisé en ce qu'une conduite (26) raccorde le récipient de réserve (18) au récipient de produit (17) par le biais d'un filtre (16).
  25. Dispositif selon la revendication 19, caractérisé en ce que les sorties des dispositifs de transport (3, 4, 5, 6, 7) débouchent dans une conduite commune, qui est raccordée à une soupape à 3 voies (12), qui est raccordée tant au générateur de 68Ge/Ga (1) qu'à l'échangeur cationique (14).
  26. Dispositif selon l'une quelconque des revendications 19 à 25, caractérisé en ce que l'ensemble du déroulement est automatisé.
  27. Dispositif selon la revendication 19, caractérisé en ce que la matrice de l'échangeur cationique (14) est choisie dans le groupe des résines de polystyrène/divinylbenzène (DVB).
  28. Utilisation du dispositif selon la revendication 19 pour concentrer et purifier des solutions de radiogallium.
  29. Utilisation du dispositif selon la revendication 19 pour purifier, réduire en volume des radio-isotopes de gallium et marquer des précurseurs de marquage avec le radio-isotope 66Ga ou 67Ga.
EP05823617A 2004-11-26 2005-11-22 Procede et dispositif pour isoler un radionucleide 68ga purifie chimiquement et radiochimiquement, et pour marquer un precurseur de marquage au moyen de ce radionucleide 68ga Expired - Lifetime EP1820197B1 (fr)

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DE102004057225A DE102004057225B4 (de) 2004-11-26 2004-11-26 Verfahren und Vorrichtung zur Isolierung eines chemisch und radiochemisch gereinigten 68Ga-Radionuklids und zum Markieren eines Markierungsvorläufers mit dem 68Ga-Radionuklid
PCT/EP2005/012471 WO2006056395A2 (fr) 2004-11-26 2005-11-22 Procede et dispositif pour isoler un radionucleide 68ga purifie chimiquement et radiochimiquement, et pour marquer un precurseur de marquage au moyen de ce radionucleide 68ga

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EP1820197A2 EP1820197A2 (fr) 2007-08-22
EP1820197B1 true EP1820197B1 (fr) 2009-09-23

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US (1) US8147804B2 (fr)
EP (1) EP1820197B1 (fr)
AT (1) ATE443916T1 (fr)
DE (2) DE102004057225B4 (fr)
DK (1) DK1820197T3 (fr)
ES (1) ES2333893T3 (fr)
WO (1) WO2006056395A2 (fr)

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DE102009049108B4 (de) 2009-10-12 2016-12-08 Johannes Gutenberg-Universität Mainz Verfahren und Vorrichtung zur Gewinnung eines Radionuklids
CA2791751C (fr) 2010-03-03 2016-11-01 Australian Nuclear Science And Technology Organisation Materiau sorbant
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DE102010037964B3 (de) * 2010-10-05 2012-03-22 ITM Isotopen Technologien München AG 68Ga-Generator
DE202010017082U1 (de) 2010-12-08 2011-05-12 ITM Isotopen Technologien München AG Vorrichtung zur Markierung von Molekülen mit Radionukliden und Verwendung derselben zur Herstellung einer radiopharmazeutischen Verbindung
ITFI20110180A1 (it) * 2011-08-12 2013-02-13 Advanced Accelerator Applic S A Processo per la preparazione di complessi di 68ga.
FR2980193B1 (fr) * 2011-09-15 2014-02-14 Guerbet Sa Procede de purification de produits de contraste
RU2464043C1 (ru) * 2011-09-26 2012-10-20 Федеральное государственное бюджетное учреждение "Федеральный медицинский биофизический центр имени А.И. Бурназяна" СПОСОБ ПОЛУЧЕНИЯ РАСТВОРОВ 68Ga ВЫСОКОЙ ЧИСТОТЫ
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JP6052681B2 (ja) * 2011-10-21 2016-12-27 国立大学法人 長崎大学 ６８Ｇｅ−６８Ｇａジェネレータおよびこれを用いる６８Ｇａ含有液の製造方法
DE102012208376C5 (de) * 2012-05-18 2018-02-01 Zentralklinik Bad Berka Gmbh Satz und Verfahren zur Herstellung eines Radiopharmakons
DE102012208377B4 (de) * 2012-05-18 2015-07-23 Zentralklinik Bad Berka Gmbh Satz und Verfahren zur Herstellung eines Radiopharmakons
US9161998B2 (en) * 2012-05-18 2015-10-20 Zentralklinik Bad Berka Gmbh Method and kit for preparing a radiopharmaceutical
DE102012208378B4 (de) * 2012-05-18 2015-07-23 Zentralklinik Bad Berka Gmbh Satz und Verfahren zur Herstellung eines Radiopharmakons
DE102012208375B4 (de) * 2012-05-18 2015-07-23 Zentralklinik Bad Berka Gmbh Satz und Verfahren zur Herstellung eines Radiopharmakons
DE102012019714B4 (de) 2012-10-08 2022-04-28 Johannes Gutenberg-Universität Mainz Verfahren zur Herstellung von pharmakologischen Metall-Ligand-Konjugaten
JP6162063B2 (ja) * 2014-03-17 2017-07-12 住友重機械工業株式会社 放射性同位元素の精製装置、及び放射性同位元素の精製方法
JP6696990B2 (ja) * 2015-01-30 2020-05-20 アドヴァンスド アッチェレラター アプリケーションズ インターナショナル ソシエテ アノニム ６８Ｇｅ／６８Ｇａジェネレーターから生じる溶離液からＧａ−６８を精製する方法および該方法において使用するためのクロマトグラフィーカラム
JP6536945B2 (ja) * 2015-06-17 2019-07-03 学校法人北里研究所 線源
PL3343570T3 (pl) 2016-12-27 2019-11-29 Itm Isotopen Tech Muenchen Ag Generator <sup>68</sup>Ge/<sup>68</sup>Ga
TW201832750A (zh) * 2017-03-02 2018-09-16 美商５１１製藥公司 放射性藥品標記裝置
CN113173595B (zh) * 2021-03-30 2023-09-15 广东回旋医药科技股份有限公司 一种回旋加速器制备的68Ga粗品的纯化方法
CN113144225A (zh) * 2021-03-30 2021-07-23 广东回旋医药科技股份有限公司 一种高放射性核纯度的68Ga-GaCl3溶液的制备方法及应用
CN116272367B (zh) * 2023-04-06 2025-07-15 中国工程物理研究院核物理与化学研究所 一种基于166Dy-166Ho发生器分离166Ho的方法

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ES2333893T3 (es) 2010-03-02
WO2006056395A2 (fr) 2006-06-01
DE502005008206D1 (de) 2009-11-05
WO2006056395B1 (fr) 2007-03-15
DE102004057225A1 (de) 2006-06-08
US8147804B2 (en) 2012-04-03
EP1820197A2 (fr) 2007-08-22
WO2006056395A3 (fr) 2007-01-25
ATE443916T1 (de) 2009-10-15
US20080277350A1 (en) 2008-11-13
DK1820197T3 (da) 2010-01-25
DE102004057225B4 (de) 2006-10-12

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