- Chemoenzymatic n.c.a synthesis of the coenzyme UDP-2-deoxy-2-( 18F)fluoro-α-D-glucopyranose as substrate of glycosyltransferases
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The development of 18F-labelling methods adopted to proteins and bioactive peptides is of great interest in radiopharmaceutical sciences. In order to provide 18F-labelled sugars as a polar prosthetic group for an enzymatic 18F-labelling procedure, an appropriate nucleotide activated sugar is needed. Here, we present the radiosynthesis of n.c.a. UDP-2-deoxy-2-[18F]fluoro-α-D-glucopyranose (UDP-[ 18F]FDG) as a substrate for glycosyltransferases. The MacDonald synthesis of [18F]FDG-1-phosphate was successfully combined with an enzymatic activation to obtain UDP-[18F]FDG directly in an aqueous medium located in the void volume of a solid phase cartridge. The radiochemical yield of UDP-[18F]FDG was 20% (based on [18F]fluoride) after a total synthesis time of 110 min. Thus, an intermediate was provided for the enzymatic transfer of [18F]FDG using UDP-[18F]FDG as glycosyl donor making use of a suitable glycosyltransferase. This would represent a highly selective and mild 18F-labelling method for glycosylated biomolecules. Copyright
- Prante, Olaf,Hamacher, Kurt,Coenen, Heinz H.
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Read Online
- A new class of SN2 reactions catalyzed by protic solvents: Facile fluorination for isotopic labeling of diagnostic molecules
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Aprotic solvents are usually preferred for the SN2 reactions, because nucleophilicity and hence SN2 reactivity are severely retarded by the influence of the partial positive charge of protic solvents. In this work, we introduce a remarkable effect of using tertiary alcohols as a reaction medium for nucleophilic fluorination with alkali metal fluorides. In this novel synthetic method, the nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts (such as alkenes, alcohols, or ethers) compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with [18F]fluorine (t1/2 = 110 min) for positron emission tomographic (PET) imaging, and it is illustrated by the synthesis of four [ 18F]fluoride-radiolabeled molecular imaging probes-[ 18F]FDG, [18F]FLT, [18F]FP-CIT, and [ 18F]FMISO-in high yield and purity and in shorter times compared to conventional syntheses.
- Kim, Dong Wook,Ahn, Doo-Sik,Oh, Young-Ho,Lee, Sungyul,Kil, Hee Seup,Oh, Seung Jun,Lee, Sang Ju,Kim, Jae Seung,Ryu, Jin Sook,Moon, Dae Hyuk,Chi, Dae Yoon
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Read Online
- SYSTEM FOR RADIOPHARMACEUTICAL PRODUCTION
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Certain embodiments of the present invention relate to a system and a method for producing a radiopharmaceutical, wherein the system is formed from and/ or provides a microfluidic flow system. In certain embodiments, the system comprises a radioisotope isolation module, a radiopharmaceutical production module, a purification module and a quality control module.
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Page/Page column 41; 44
(2016/06/06)
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- DEVICE AND METHOD FOR THE PRODUCTION OF RADIOCHEMICAL COMPOUNDS
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The invention relates to a device for the preparation of radiochemical compounds. It is provided that the device comprises at least a reaction module, a dosing module, and a storage module, wherein the reaction module has at least one reaction vessel having a closable opening through which substances needed for the preparation of a predetermined radiochemical compound can be introduced into the reaction vessel of the reaction module and through which the prepared radiochemical compound can be removed from the reaction vessel of the reaction module;the dosing module has at least one pipetting head which can be moved relative to the storage module and the reaction module and in x, y, and z directions and also has at least one dosing unit; andat least one reservoir for one of the substances needed for the preparation of the respective radiochemical compound is formed in the storage module.
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Paragraph 0093-0094
(2015/05/26)
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- DUAL RUN CASSETTE FOR THE SYNTHESIS OF 18F-LABELLED COMPOUNDS
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The invention provides a new chemical process, a new cassette configuration, and new software. The invention allows one synthesizer in one hot cell to produce sequentially two batches of [18F]-labelled PET tracer in the same day.
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Page/Page column 15-17
(2015/06/03)
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- MODULAR RADIOCHEMISTRY SYNTHESIS SYSTEM
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A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the positi
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Paragraph 0291-0295
(2016/01/15)
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- System, device and method for preparing tracers and transferring materials during radiosynthesis
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A system, apparatus, and method for transferring chemical solutions and synthesizing a tracer. For transferring chemical solutions, the system comprises a primary container; a secondary container; a first line in communication with the primary container a
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Paragraph 0130-0131
(2014/11/13)
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- 3,4,6-Tri-O-acetyl-1,2-O-[1-(exo-ethoxy)ethyl-idene]-Β-d-manno- pyranose 0.11-hydrate
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The title compound, C16H24O10·0. 11H2O, is a key inter-mediate in the synthesis of 2-de-oxy-2-[ 18F]fluoro-d-glucose (18F-FDG), which is the most widely used mol-ecular-imaging probe for positron emission tomography (PET). The crystal structure has two independent mol-ecules (A and B) in the asymmetric unit, with closely comparable geometries. The pyran-ose ring adopts a 4 C 1 conformation [Cremer-Pople puckering parameters: Q = 0.553 (2) A?, = 16.2 (2)° and = 290.4 (8)° for mol-ecule A, and Q = 0.529 (2) A?, =15.3 (3)° and = 268.2 (9)° for mol-ecule B], and the dioxolane ring adopts an envelope conformation. The chiral centre in the dioxolane ring, introduced during the synthesis of the compound, has an R configuration, with the eth-oxy group exo to the manno-pyran-ose ring. The asymmetric unit also contains one water mol-ecule with a refined site-occupancy factor of 0.222 (8), which bridges between mol-ecules A and B via O - H?O hydrogen bonds.
- Liu, Ya-Ling,Zou, Pei,Wu, Hao,Xie, Min-Hao,Luo, Shi-Neng
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p. o338-o340
(2012/11/13)
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- Homogeneous nucleophilic radiofluorination and fluorination with phosphazene hydrofluorides
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A series of phosphazenium hydrofluorides, P1 tBu·[18/19F]HF, P1 tOct·[18/19F]HF, P2Et· [18/19F]HF, and P4tBu·[ 18/19F]HF, was synthesized. The radioactive phosphazenium [ 18F]hydrofluorides were obtained by the one-step formation and trapping of gaseous [18F]HF with the respective phosphazene bases. The [19F] isotopomers were prepared from the corresponding phosphazene bases and Et3N·3HF. Under the design of experiment (DoE)-optimized conditions, P2Et·HF and P 4tBu·HF fluorinated alkyl chlorides, bromides, and pseudohalides in 76-98 % yield, but gave lower yields with iodides and electron-deficient arenes. DoE models showed that fluorination can be performed in glass vessels, and that the reactivity of P2Et· HF and P4tBu·HF is dominated by solvent polarity but is insensitive to water to at least 2 equiv. In contrast, P1 tBu·HF and P1tOct·HF were unstable towards autofluorolysis. DFT calculations were performed to rationalize this finding in terms of diminished steric bulk, higher Parr's electrophilicity, and chemical hardness of P1RH +. The corresponding radiofluorination reaction gave no valid DoE model but displayed similar substrate scope. High specific activity and excellent radiochemical yields with various pseudohalides (81-91 %) suggest that the proposed radiofluorination methodology can complement the current [ 18F]KF/Kryptofix methods, particularly in the areas for which nonpolar reaction conditions are required. A tale of fluoride: Up to 82 % of [18F]fluoride can be recovered from aqueous solution as [ 18F]HF gas in just one step (see scheme; Tf: trifluoromethanesulfonyl, Ms: methanesulfonyl, Ts=p-toluenesulfonyl). Trapped as phosphazenium hydrofluorides, 18F- and 19F- isotopomers attain high nucleophilicity and solubility in nonpolar solvents. Excelling in fluorination and radiofluorination of various pseudohalides, their substrate scope also extends to halides and nitroarenes. Copyright
- Mathiessen, Bente,Jensen, Andreas T. I.,Zhuravlev, Fedor
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experimental part
p. 7796 - 7805
(2011/08/22)
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- Synthesis of the positron-emitting radiotracer [18F]-2-fluoro-2- deoxy-d-glucose from resin-bound perfluoroalkylsulfonates
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A new approach to the synthesis of 2-fluoro-2-deoxy-d-glucose (FDG, [ 19/18F]-3) is described, which employs supported perfluoroalkylsulfonate precursors 33-36, where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [ 19F]fluoride ion afforded protected FDG [19F]-18 as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [19F]-18 was shown to produce [19F]FDG. The method has been applied to the efficient radiosynthesis of the imaging agent [18F]FDG, and was shown to produce the radiochemical tracer in good radiochemical yield (average 73%, decay corrected). The Royal Society of Chemistry 2009.
- Brown, Lynda J.,Ma, Nianchun,Bouvet, Denis R.,Champion, Sue,Gibson, Alex M.,Hu, Yulai,Jackson, Alex,Khan, Imtiaz,Millot, Nicolas,Topley, Amy C.,Wadsworth, Harry,Wynn, Duncan,Brown, Richard C. D.
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experimental part
p. 564 - 575
(2009/07/18)
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- PROCESS FOR PRODUCTION OF COMPOUND LABELED WITH RADIOACTIVE FLUORINE
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A process for production of 18F-FDG is provided, which can produce 18F-FDG in a high and stable yield of synthesis. A process for production of a compound labeled with radioactive fluorine comprises the steps of: preparing a reaction solution by adding, under a hermetic condition, TATM and an inert organic solvent to a mixture containing [18F]fluoride ions, a phase transfer catalyst and potassium ions; giving a reaction condition to the reaction solution under a hermetic condition to obtain 18F-TAFDG; and subjecting the obtained 18F-TAFDG to a deprotection process and optionally to a purification process to obtain 18F-FDG.
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(2008/12/07)
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- A solid-phase route to 18F-labeled tracers, exemplified by the synthesis of [18F]2-fluoro-2-deoxy-D-glucose
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(Chemical Equation Presented) Scintillating synthesis: 18F- Containing radiopharmaceuticals can be prepared by using [18F] fluoride ions to displace a sulfonate linker and release a radiotracer from a solid support (see scheme; EOM =
- Brown, Lynda J.,Bouvet, Denis R.,Champion, Sue,Gibson, Alex M.,Hu, Yulai,Jackson, Alex,Khan, Imtiaz,Ma, Nianchun,Millot, Nicholas,Wadsworth, Harry,Brown, Richard C. D.
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p. 941 - 944
(2008/02/01)
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- FLUORIDATION PROCESS
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The invention relates to an improved process for the fluoridation of sugar derivatives in which a controlled amount of water is present in the solvent.
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Page/Page column 12
(2008/06/13)
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- METHOD OF DEPROTECTION
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The invention provides a method for the synthesis of an 18F-labelled product comprising deprotected of a protected 18F-labelled compound using a deprotection agent comprising a weak acid and wherein neutralisation and buffering of the deprotected product are carried out by the addition of a neutralisation agent. The deprotected product is buffered in a pH range suitable for subsequent autoclaving and formulation into an injectable radiopharmaceutical.
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(2008/06/13)
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- METHOD FOR PREPARATION OF ORGANOFLUORO COMPOUNDS IN ALCOHOL SOLVENTS
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The present invention relates to a method for preparation of organofluoro compounds containing radioactive isotope fluorine- 18. More particularly, the present invention relates to a method for preparation of organofluoro compound by reacting fluorine salt containing radioactive isotope fluorine- 18 with alkyl halide or alkyl sulfonate in the presence of alcohol of Chemistry (Figure 1) as a solvent to obtain high yield of organofluoro compound. Synthesis reaction according to the present invention may be carried out under mild condition to give high yield of the organofluoro compounds and the reaction time is decreased, and thereby is suitable for the mass production of the organofluoro compounds.
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(2008/06/13)
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- Microfluidic apparatus and method for synthesis of molecular imaging probes including FDG
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The invention provides a method and apparatus for preparation of radiochemicals wherein the reaction that couples the radioactive isotope to the reactive precursor to form a positron-emitting molecular imaging probe is performed in a microfluidic environm
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Page/Page column 11
(2008/06/13)
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- A new synthesis of FDG, suitable for Regional Distribution, with Productions of over 2 Ci FDG, using the FDG MicroLab.
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A new synthesis of FDG, suitable for regional distribution, in productions of over 2 Ci FDG has been developed for the FDG MicroLab.The new method has shortened the synthesis time to 40percent, with an RCP > 95percent, and an acetonitrile content of the final product of 100 ppm.The new method is of Hamacher type, using Tetra Butyl Ammonium di-hydrogen phosphate (TBA) as Phase Transfer Reagent (PTR), and also, in an acetonitrile/water solution for elution of 18F- from the 18O-water-recycling column.The hydrolysis has been changed to run under basis conditions using 0.1 M NaOH.The Content of FDM in the final product is 1percent.
- Ulin, Johan,Dahlstroem, Kent,Kiselev, Maxim
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p. 330 - 331
(2007/10/03)
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- SYNTHESIS OF 2-DEOXY-2-FLUOROHEXOSES BY FLUORINATION OF GLYCALS IN AQUEOUS MEDIA
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1,5-Anhydro-2-deoxy-D-arabino- (D-glucal), 1,5-anhydro-2-deoxy-D-lyxo- (D-galactal), and 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-lyxo-hex-1-enitol (3,4,6-tri-O-acetyl-D-galactal) (3) were fluorinated in water and organic solvent-water with molecular fluorine and, for 18F-labelled compounds, with 18F>fluorine.Chemical yields of 40 and 10percent were obtained for 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose, respectively, and 35 and 5percent for 2-deoxy-2-fluoro-D-galactose (12) and 2-deoxy-2-fluoro-D-talose (13), respectively.In the fluorination of 3, the chemical yields of 12 and 13 were 38 and 6percent, respectively.An l.c. separationof 2-deoxy-2-fluoro-D-hexoses is described.
- Diksic, Mirko,Jolly, Dean
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- SYNTHESIS OF SOME 2-DEOXY-2-FLUOROHEXOPYRANOSES, POTENTIAL DIAGNOSTIC IMAGING AGENTS
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2-Deoxy-2-fluoro-D-galacto-, -D-altro-, and -L-gluco-pyranose have been prepared by the reactions of corresponding glycals with fluorine gas followed by acidic hydrolysis, respectrively.The gas was produced by the 20Ne(d, α)18F nuclear reaction using the cyclotron.D-Galactopyranose derivative showed markedly diagnostic liver-imaging activity.
- Tada, Masao,Matsuzawa, Taiju,Ohrui, Hiroshi,Fukuda, Hiroshi,Ido, Tatsuo,et al.
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p. 565 - 568
(2007/10/02)
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- A synthesis of 2-deoxy-2-fluoro-D-glucose using accelerator-produced 18F-fluoride ion generated in a water target
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A synthesis of of 2-deoxy-2-fluoro-D-glucose ("-DFG) from 1,2-anhydro-3,4:5,6-di-O-isopropylidene-1-C-nitro-D-mannitol has been developed.Tehe procedure employed 18F produced by the 16O(3He,p)18F reaction using a water target.The label was introduced using KHF2 dried by microwave heating; the 18F-labeled derivative, upon treatment with 80percent trifluoroacetic acid, afforded 2-DFG in a radiochemical yield of 10percent.The total time of the synthesis was less than 110 min.
- Beeley, Philip A.,Szarek, Walter A.,Hay, George W.,Perlmutter, Milton M.
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p. 2709 - 2711
(2007/10/02)
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- Direct Displacement with Anhydrous Fluoride of the C-2 Trifluoromethanesulfonate of Methyl 4,6-O-Benzylidene-3-O-methyl-2-O-trifluoromethylsulfonyl-β-D-mannopyranoside
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A displacement reaction with 18F-caesium fluoride (anhydrous) was employed to label 2-deoxy-2-fluoro-D-glucose.
- Levy, Shlomo,Livni, Eli,Elmaleh, David,Curatolo, William
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p. 972 - 973
(2007/10/02)
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