EP1287532A2 - Procede pour produire un ion fluorure ?18 f] - Google Patents

Procede pour produire un ion fluorure ?18 f]

Info

Publication number
EP1287532A2
EP1287532A2 EP01941492A EP01941492A EP1287532A2 EP 1287532 A2 EP1287532 A2 EP 1287532A2 EP 01941492 A EP01941492 A EP 01941492A EP 01941492 A EP01941492 A EP 01941492A EP 1287532 A2 EP1287532 A2 EP 1287532A2
Authority
EP
European Patent Office
Prior art keywords
fluoride ion
chamber
produced
reactive
oxygen gas
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Withdrawn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
EP01941492A
Other languages
German (de)
English (en)
Other versions
EP1287532A4 (fr
Inventor
Jorge R. Barrio
Nagichettiar Satyamurthy
Michael E. Phelps
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.)
University of California
University of California Berkeley
University of California San Diego UCSD
Original Assignee
University of California
University of California Berkeley
University of California San Diego UCSD
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 University of California, University of California Berkeley, University of California San Diego UCSD filed Critical University of California
Publication of EP1287532A2 publication Critical patent/EP1287532A2/fr
Publication of EP1287532A4 publication Critical patent/EP1287532A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
    • G21G1/10—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators by bombardment with electrically charged particles

Definitions

  • the present invention is directed to methods for producing [' 8 F] fluoride ion, and more particularly, methods for producing [ 18 F] fluoride ion using [ 18 O]oxygen gas.
  • Positron emission tomography is a unique diagnostic imaging modality that measures the time-dependent localized concentrations of radiopharmaceuticals labeled with position-emitting radionuclides within the human body.
  • Fluorine- 18 is used in the preparation of radiopharmaceuticals, such as 2-deoxy-2[ 18 F]fluoro-D-glucose (FDG), for PET imaging determinations.
  • FDG 2-deoxy-2[ 18 F]fluoro-D-glucose
  • Fluorine- 18 labeled fluoride ion has found widespread use in the synthesis of FDG for clinical use, but it is also used to produce a wide variety of other PET biological probes for research and clinical investigations of the brain, heart, and in the diagnosis of cancer.
  • Fluorine- 18 is commonly produced by proton irradiation of the stable oxygen- 18 isotope according to the 18 O(p,n) 18 F nuclear reaction.
  • fluorine- 18 labeled precursors used for the synthesis of 18 F-labeled radiopharmaceuticals for research and clinical PET imaging, namely, [ 18 F]fluoride ion and [ 18 F]fluorine gas.
  • Fluoride ion is generally used in nucleophilic substitution reactions, and fluorine gas is used in electrophilic reactions.
  • [ 18 F]fluoride ion is typically produced using liquid [ 18 O]water as the target material, and [ 18 F] fluorine gas is typically produced using [ 18 O]oxygen.
  • the standard method for the cyclotron production of aqueous [ 18 F]fluoride ion is by irradiation of [ 18 O]water using low-energy (10-17 MeN) protons according to the nuclear reaction 18 O(p,n) 18 F. (See Ruth, TJ. and Wolf, A.P. (1979), Absolute cross sections of the production of 18 F via the 18 O(p,n) 18 F reaction. Radiochim. Ada 26, 21-24.)
  • This reaction which uses the stable isotope oxygen-18 as the target material, offers a significantly higher yield than older deuterons-on-neon methods, giving about 188 mCi/ ⁇ A yield at saturation for 11 MeN protons.
  • the typical [ 18 O] water target holds about 0.35 to 1.2 mL of water, and using 20-30 ⁇ A beam current will easily yield cure-levels of [ 18 F] fluoride ion for a 60-120 minute bombardment.
  • this method suffers several drawbacks, including (I) the cost of the [ 18 O] ater (currently about $175/gram for 97% enriched, and $234/gram for 99% enriched), (ii) the limited availability of [ 18 O]water and the dependence of PET centers on foreign sources for the supply of this critical raw material, and (iii) target reliability and yield issues.
  • the [ 18 O]water is either separated from the [ 18 F] fluoride ion using a small trap-and-release anion exchange column with the recovered [ 18 O] water, containing metallic cations, being collected and saved, or is simply evaporated and lost as the first step in the radiochemical labeling process.
  • FDAMA Food and Drug Modernization Act
  • the present invention is directed to a method for producing [ I8 F]fluoride ionfrom [ 18 O]oxygen gas that attempts to address the drawbacks of the prior art.
  • the method comprises first loading an enclosed chamber of a metal target with [ 18 O]oxygen gas.
  • the [ 18 O]oxygen gas in the chamber of the metal target is irradiated to produce [ 18 F]fluoride ion in the chamber.
  • the produced [ 18 F] fluoride ion is removed from the chamber without opening the target.
  • the invention provides remote, automated recovery of reactive [ ! 8 F]fluoride ion with easy release of the [ 18 F]fluoride ion from the metal target surface.
  • the thereby recovered [ ls F]fluoride ion can be used in the synthesis of [ 18 F]labeled radiopharmaceuticals, typically by nucleophilic displacement using appropriate precursor substrates, and other radiolabeled compounds.
  • the invention is directed to a method for producing [ 18 F]fluoride ion.
  • the method comprises loading an enclosed chamber of a metal target with [ 18 O]oxygen gas.
  • the [ 18 O]oxygen gas is irradiated in the enclosed chamber to produce [ 18 F]fluoride ion in the chamber.
  • a solubilizing agent is introduced into the enclosed chamber, without opening the target, to solubilize produced [ 18 F]fluoride ion.
  • the solubilizing agent and produced [ 18 F]fluoride ion are removed from the enclosed chamber without opening the target.
  • the method of the invention offers several important advantages over the use of liquid [' 8 O] water.
  • gas targets are able to withstand relatively higher beam currents than small-volume [ l8 O] water targets, which translates to higher product yields and more reliable operation.
  • the [ 18 O]oxygen gas target material can also be efficiently recovered after the bombardment and can be recycled for subsequent runs.
  • the methods of the invention are superior to the method disclosed by Nickles et al. in that the present methods provide remote, automated recovery of the [ 18 F]fiuoride ion, thereby minimizing contact with radioactivity.
  • the methods of the invention benefit PET. Specifically, clinical radiopharmaceuticals such as FDG can be produced in higher yields, which means extended availability for patients at lower cost. Further, the inventive methods make available to distribution centers low-cost [ 18 F] fluoride ion, which is an important tool that will make available to molecular biology researchers a large number of biological probes, such as 3'-deoxy-3'[ I8 F]fluorothymidine (FLT) for tumor proliferation, 9-(4- [ 18 F]fluoro-3-hydroxymethyl-butyl)guanine ([ 18 F]fluoropeniciclovir, FHBG) for gene expression, and a variety of compounds for receptor imaging and other investigations.
  • FLT 3'-deoxy-3'[ I8 F]fluorothymidine
  • FHBG 9-(4- [ 18 F]fluoro-3-hydroxymethyl-butyl)guanine
  • FIG. 1 is a side cross-sectional view of a metal target for use in connection with the present invention.
  • FIG. 2 is an end view of the metal target of FIG. 1. °
  • the present invention is directed to methods for producing [ l 8 F]fluoride ion from [ 18 O]oxygen gas in a metal target.
  • FIGs. 1 and 2 A suitable metal target for use in connection with the present invention is depicted in FIGs. 1 and 2.
  • the metal target has a generally cylindrical sidewall 10, a proximal end wall 12, and a distal end wall 14, which together form a chamber 16.
  • the chamber 16 is preferably conical-shaped (10 mm diameter entrance tapering to 15 mm at the back) with a 15 mL volume.
  • the chamber 16 has an inner wall 18 made of a suitable metal, i.e., a metal from which [ 18 F]fluoride ion can be removed.
  • suitable metals for use in connection with the invention include, but are not limited to, nickel, silver, copper, gold, tantalum, stainless steel, titanium, and alloys thereof, as well as one of these metals plated with another of these metals, e.g., gold-plated copper.
  • Particularly preferred target materials include high purity electroform nickel and nickel- 200.
  • the proximal end wall 12 of the target is connected to a suitable cyclotron (not shown).
  • a preferred cyclotron for use in connection with the present invention is an RDS-112 negative ion cyclotron, commercially available from CTI.
  • [ 18 O]oxygen gas is loaded in the enclosed chamber 16 through an oxygen valve 20 to a suitable pressure.
  • the [ I8 O]oxygen gas is loaded to a pressure of about 200 to about 220 psi.
  • the [ 18 O]oxygen gas is irradiated with high energy protons from the cyclotron.
  • the protons preferably have an energy greater than 5 MeN, preferably from about 5 to about 16 MeN.
  • the protons pass from the cyclotron through a passage 21 in the proximal end wall 12 at about 10 to about 60 ⁇ A for a time period ranging from about 10 minutes to about 2 hours to produce [ 18 F]fluoride ion on the walls of the chamber.
  • the [ 18 O]oxygen gas is removed from the chamber 16 through the oxygen valve 20 and cryorecovered for subsequent reuse.
  • the cyclotron is kept under high vacuum, while the chamber 16 is maintained at a pressure.
  • An aluminum vacuum foil 22 and a havar target foil 24 are provided within the passage 21 between the cyclotron and the chamber 16 to maintain the pressure differential .
  • an inert gas such as helium, neon, nitrogen or argon, is passed through a cooling passage 25 that runs between the foils.
  • the irradiation also generates a significant amount of heat in the chamber 16 due to the protons being passed through the metal target.
  • a water cooling jacket 26 is provided within the sidewall 10 to maintain the chamber at a temperature ranging from about 12°C to about 17°C, with 12° to 15 °C water being passed through the jacket.
  • a suitable liquid solubilizing agent is introduced into the enclosed chamber of the metal target for removal of the [ ,8 F]fluoride ion.
  • Suitable solubilizing agents for use in connection with the present invention include water, aqueous salt solutions, organic solvents, organic acids and their solutions in water or an organic solvent, and combinations thereof.
  • aqueous salt solutions include ⁇ aOH, ⁇ a 2 CO 3 , NaHCO 3 , sodium oxalate, sodium acetate, sodium propionate, sodium butyrate, sodium succinate, sodium benzoate, sodium tatrate, sodium lactate; KOH, K 2 CO 3 , KHCO 3 , potassium oxalate, potassium acetate, potassium propionate, potassium butyrate, potassium succinate, potassium benzoate, potassium tartrate, potassium lactate; RbOH, Rb 2 CO 3 , RbHCO 3 , rubidium oxalate, rubidium acetate, rubidium propionate, rubidium butyrate, rubidium succinate, rubidium benzoate, rubidium tartrate, rubidium lactate; CsOH, Cs 2 CO 3 , CsHCO 3 , cesium oxalate, cesium acetate, cesium propionate, cesium butyrate, cesium succinate, cesium benzoate, cesium tartrate,
  • suitable organic solvents include lower aliphatic alcohols such as methanol, ethanol, propanol, isopropanol, butanol, s-butanol, t-butanol; aromatic compounds such as benzyl alcohol, phenol, cresols; ethers such as tetrahydrofuran, dioxane; acetonitrile; dimethylformamide; dimethylsulfoxide; trifluoroethanol; hexafluoroisopropanol; hexamethylphosphorictriamide; pyridine; chloroform; and combinations thereof.
  • lower aliphatic alcohols such as methanol, ethanol, propanol, isopropanol, butanol, s-butanol, t-butanol
  • aromatic compounds such as benzyl alcohol, phenol, cresols
  • ethers such as tetrahydrofuran, dioxane
  • acetonitrile dimethylformamide
  • Suitable organic acids include acetic acid, propionic acid, oxalic acid, succinic acid, butyric acid, valeric acid, tartaric acid, lactic acid, benzoic acid ethylenediamine tetraacetic acid and combinations thereof.
  • the metal target is closed so that the chamber 16 remains enclosed to prevent the user from contact with radioactivity.
  • the solubilizing agent is introduced into the enclosed chamber of the metal target through a liquid fill port 28 without opening the target.
  • the solubilizing agent is allowed to remain in the chamber 16 for a time sufficient to remove most of the [ 18 F]fluoride ion from the metal target, preferably for a period of time ranging from about 10 seconds to about 10 minutes.
  • the temperature of the chamber should be kept below the boiling point of the solubilizing agent, and preferably maintained at a temperature ranging from about 4°C to about 100°, more preferably from about 25 °C to about 100°C.
  • the solubilizing agent is removed from the enclosed chamber through a liquid recovery port 30 by, for example, pressurizing the chamber with an inert gas, such as helium, argon, neon, or nitrogen.
  • the gas is introduced into the chamber 16 through a gas port 32 and removed from the chamber through the liquid recovery port 30.
  • the solubilizing agent is passed through a suitable exchange resin cartridge, preferably an anion exchange resin cartridge, to trap the [ 18 F]fluoride ion thereon.
  • the [ 18 F]fluoride ion is eluted off the resin cartridge with a suitable eluting agent.
  • Particularly preferred eluting agents include inorganic and organic salt solutions, such as potassium carbonate, potassium oxalate, potassium hydroxide, potassium bicarbonate, tetraalkylammonium bicarbonate (preferably lower alkyl, such as methyl, ethyl, propyl or butyl), tetraalkylammonium carbonate, tetraalkylammonium hydroxide, and combinations thereof.
  • inorganic and organic salt solutions such as potassium carbonate, potassium oxalate, potassium hydroxide, potassium bicarbonate, tetraalkylammonium bicarbonate (preferably lower alkyl, such as methyl, ethyl, propyl or butyl), tetraalkylammonium carbonate, tetraalkylammonium hydroxide, and combinations thereof.
  • the solubilizing agent can be evaporated to isolate the [ 18 F]fluoride ion.
  • the target is cleaned for use.
  • a preferred method for cleaning the target involves flushing with water followed by an organic solvent, such as methanol, through the chamber 16.
  • the water and solvent are introduced into and removed from the chamber 16 through the liquid fill port 28 and liquid recovery port 30, respectively.
  • an inert gas such as helium, argon, neon or nitrogen, is passed through the chamber 16.
  • the inert gas is introduced through the gas port 32 and removed through the liquid recovery port 30.
  • an insert can be placed into the chamber so that the [ 18 F]fluoride ion deposits onto the insert.
  • the insert can be made of treated glass (e.g., glass plated with silver or another metal), such as is described in aforementioned Nickles et al. reference, or the insert can be made of a suitable metal, such as those set forth above.
  • the [ 18 F] fluoride ion is removed from the chamber while the target is closed.
  • the methods of the present invention can be used to produce reactive
  • [ 18 F]fluoride ion for use in the production of a number of radiolabeled compounds including 2 -deoxy-2 [ I 8 F] fluoro -D -glucose(FDG) , 2 -( l - ⁇ 6 - [2 - [ 18 F]fluoroethyl(methyl)amino]-2-naphthyl ⁇ ) ethylidenemalono-nitrile ( 18 F-FDDNP), 2'- [ 18 F]fluoroethylspiperone( 18 F-FESP), 3'-deoxy-3'-[ 18 F]fluorothymidine( 18 F-FLT), 9-[(3- [ 18 F]fluoro-l-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG), 9-(4-[ 18 F]fluoro-3- hydroxymethylbutyl)guanine ([ 18 F]FHBG), [ 18 F]fluorobromomethane,
  • a small anion exchange cartridge (such as an Accell QMA Plus, commercially available from Waters Associates and activated with 1.0 M potassium bicarbonate solution) is used to trap the [ I8 F] -fluoride ion released from the target.
  • the [ I8 F] -fluoride ion is eluted off the cartridge with 0.4 mL of K 2 CO 3 solution (0.04 M), and Kryptofix 222 (10-20 mg) is added.
  • the aqueous solution is evaporated at 115 °C with a stream of dry nitrogen, and further moisture is removed by azeotropic distillation with acetonitrile (3 x 1 mL).
  • One mL of 1.0 N hydrochloric acid is added to the residue and heated at 115 °C for 10 to 15 min.
  • the hydrolyzed mixture is then transferred onto the top of a column of ion-retardation resin (Bio-Rad, AG11 A8, 50-100 mesh) pre-equilibrated with sterile water.
  • the hydrolysis vessel is rinsed with water (10-20 mL) onto the column, and the FDG that is eluted from the column is passed through tandem Classic alumina and C-18 Sep-Pak cartridges (available from Waters Associates) which have been washed with absolute ethanol (5 to 10 mL) followed by sterile water (10 to 20 mL).
  • the resulting solution is sterilized by passing through a Millipore filter (0.22 ⁇ M) into a sterile 30 mL multi-injection vial containing appropriate amounts of sodium chloride to make the final solution isotonic.
  • the activity of the FDG is measured using a dose calibrator (such as a CRC-3512 commercially available from Capintec Inc.) and corrected to the end of bombardment (EOB). This activity is compared to the activity of 18 F-fluoride released from the target (corrected to EOB) to determine the yield of FDG produced.
  • the term “5% reactive” indicates that the [ I8 F]fluoride ion can be converted to FDG in a 5% yield
  • the term “10% reactive” indicates that the [ 18 F]fluoride ion can be converted to FDG in a 10% yield
  • the term “20% reactive” indicates that the [ 18 F] fluoride ion can be converted to FDG in a 20% yield
  • the [ 18 F]fluoride ion produced in accordance with the inventive methods is at least about 5% reactive, more preferably at least about 10% reactive, even more preferably at least about 20% reactive, still more preferably at least about 30% reactive, yet more preferably at least about 50% reactive, even more preferably at least about 70% reactive, as shown in Tables I and II of the Examples below.
  • a 15 mL volume, conical-shaped (10 mm diameter entrance tapering to 15 mm at the back) metal target was provided.
  • the metal used for each target is set forth in Table I.
  • [ 18 O]oxygen gas was loaded in the target to a pressure of about 210 to 215 psi and irradiated with 11 MeN protons at 40 ⁇ A for 1 hour with an RDS- 112 cyclotron.
  • the [ 18 O]oxygen gas was then cryorecovered with an efficiency of >99% for subsequent reuse.
  • the target was filled with 15 mL of water to solubilize [ 18 F]fluoride ion from the walls of the target body.
  • Kryptof ⁇ x 222 (10-20 mg) was added. The aqueous solution was evaporated at 115 ° C with a stream of dry nitrogen and further moisture was removed by azeotropic distillation with acetonitrile (3 x 1 mL). A solution of 1 ,3 ,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl- ⁇ -D-mannopyranose (10-25 mg) in acetonitrile (1.0-2.0 mL) was added to the dry K 18 F/Kryptofix complex, and the reaction mixture was heated for 5 to 15 minutes at 85 ° C .
  • the fluorinated product solution was passed through a Classic silica Sep-Pak cartridge and eluted with ether (5 to 15 mL). The eluent was evaporated with a stream of nitrogen in a glass vessel kept at 100° to ll5°C. One mL of 1.0 N hydrochloric acid was added to the residue and heated at 115 °C for 10 to 15 min. The hydrolyzed mixture was then transferred onto the top of a column of ion-retardation resin (Bio-Rad, AG11A8, 50-100 mesh) pre-equilibrated with sterile water.
  • ion-retardation resin Bio-Rad, AG11A8, 50-100 mesh
  • the hydrolysis vessel was rinsed with water (10-20 mL) onto the column, and the FDG that was eluted from the column was passed through tandem Classic alumina and C-18 Sep-Pak cartridges (available from Waters Associates) which had been washed with absolute ethanol (5 to 10 mL) followed by sterile water (10 to 20 mL).
  • the resulting solution was sterilized by passing through a Millipore filter (0.22 ⁇ M) into a sterile 30 mL multi-injection vial containing appropriate amounts of sodium chloride to make the final solution isotonic.
  • a 15 mL volume, conical-shaped (10 mm diameter entrance tapering to 15 mm at the back) metal target was provided.
  • the metal used for each target is set forth in Table II.
  • [ 18 O]oxygen gas was loaded in the target to apressure of about 210 to 215 psi in and irradiated with 11 MeN protons at 40 ⁇ A for 1 hour with an RDS-112 cyclotron.
  • the [ 18 O]oxygen gas was then cryorecovered with an efficiency of >99% for subsequent reuse.
  • the target was filled with 15 mL of a solubilizing agent as set forth in Table II to solubilize [ 18 F]fluoride ion from the walls of the target body.

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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 Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Abstract

L'invention concerne un procédé pour produire un ion fluorure [18F], consistant à charger une chambre hermétique d'une cible métallique avec un gaz oxygène [18O] qui est irradié dans ladite chambre pour produire un ion fluorure [18F] dans cette dernière. Ce procédé consiste également à retirer cet ion fluorure [18F] de la chambre sans ouvrir la cible, de préférence par introduction d'un agent solubilisant dans la chambre hermétique afin de solubiliser l'ion fluorure [18F], et à retirer l'agent solubilisant et l'ion fluorure [18F] produit de la chambre hermétique sans ouvrir la cible. Le gaz oxygène [18O] restant est retiré de la chambre pour être réutilisé avant le retrait de l'ion fluorure [18F] de la chambre. L'ion fluorure [18F] produit est réactif et peut être utilisé pour produire des composés radiomarqués tels que le 2-désoxy-2[18F]fluoro-D-glucose.
EP01941492A 2000-05-17 2001-05-16 Procede pour produire un ion fluorure ?18 f| Withdrawn EP1287532A4 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US584839 1996-01-11
US20495200P 2000-05-17 2000-05-17
US204952P 2000-05-17
US58483900A 2000-05-31 2000-05-31
PCT/US2001/015921 WO2001087235A2 (fr) 2000-05-17 2001-05-16 Procede pour produire un ion fluorure [18f]

Publications (2)

Publication Number Publication Date
EP1287532A2 true EP1287532A2 (fr) 2003-03-05
EP1287532A4 EP1287532A4 (fr) 2006-10-25

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EP01941492A Withdrawn EP1287532A4 (fr) 2000-05-17 2001-05-16 Procede pour produire un ion fluorure ?18 f|

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Country Link
EP (1) EP1287532A4 (fr)
JP (1) JP2003536055A (fr)
AU (1) AU2001274843A1 (fr)
WO (1) WO2001087235A2 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7018614B2 (en) * 2002-11-05 2006-03-28 Eastern Isotopes, Inc. Stabilization of radiopharmaceuticals labeled with 18-F
DE102005061560A1 (de) 2005-12-22 2007-07-05 Siemens Ag Verfahren zur Herstellung von radioaktiven Isotopen für die Positronen-Emissions-Tomographie
EP2046686A1 (fr) 2006-08-03 2009-04-15 Hammersmith Imanet, Ltd Procédé de séchage de fluorure
US20090274603A1 (en) * 2006-12-06 2009-11-05 Colin Steel Non-aqueous extraction of [18f] fluoride from cyclotron targets
WO2015175972A2 (fr) 2014-05-15 2015-11-19 Mayo Foundation For Medical Education And Research Cible en solution pour la production en cyclotron de métaux radioactifs
JP6274689B1 (ja) * 2016-11-16 2018-02-07 株式会社京都メディカルテクノロジー Ｒｉ標識化合物製造装置及びｒｉ標識化合物製造方法
CN111574316A (zh) * 2020-04-28 2020-08-25 新华锦集团有限公司 用于制造ri标记化合物的制造方法及制造装置
JP6873381B1 (ja) * 2020-12-19 2021-05-19 株式会社京都メディカルテクノロジー １８ｆ標識化合物製造装置及び１８ｆ標識化合物製造方法
CN113801173B (zh) * 2021-09-24 2024-03-12 上海安迪科正电子技术有限公司 一种氟-18标记的脱氧葡糖注射液的制备方法及应用
CN117062296B (zh) * 2023-08-14 2024-02-02 北京恒益德科技有限公司 一种18f氟化钠半自动制备装置

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AU2001239816B2 (en) * 2000-02-23 2005-01-27 The University Of Alberta, The University Of British Columbia, Carleton University, Simon Fraser University, The University Of Victoria Doing Business As Triumf System and method for the production of 18F-fluoride

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WO2001087235A2 (fr) 2001-11-22
AU2001274843A1 (en) 2001-11-26
EP1287532A4 (fr) 2006-10-25
WO2001087235A3 (fr) 2002-05-30
JP2003536055A (ja) 2003-12-02

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