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1.
《Journal of labelled compounds & radiopharmaceuticals》2002,45(7):583-590
Synthesis of 2′‐deoxy‐2′‐[18F]fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([18F]‐FMAU) is reported. 2‐Deoxy‐2‐[18F]fluoro‐1,3,5‐tri‐O‐benzoyl‐α‐D‐arabinofuranose 2 was prepared by the reaction of the respective triflate 1 with tetrabutylammonium[18F]fluoride. The fluorosugar 2 was converted to its 1‐bromo‐derivative 3 and coupled with protected thymine 4 . The crude product mixture ( 5a and 5b ) was hydrolyzed in base and purified by HPLC to obtain the radiolabeled FMAU 6a . The radiochemical yield of 6a was 20–30% decay corrected (d.c.) in four steps with an average of 25% in four runs. Radiochemical purity was >99% and average specific activity was 2300 mCi/μmol at the end of synthesis (EOS). The synthesis time was 3.5–4.0 h from the end of bombardment (EOB). Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
2.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(13):941-950
The synthesis of a pyrimidine analog, 3′‐deoxy‐3′‐[18F]‐fluoro‐1‐β‐D ‐xylofuranosyluracil ([18F]‐FMXU) is reported. 5‐Methyluridine 1 was converted to its di‐methoxytrityl derivatives 2 and 3 as a mixture. After separation the 2′,5′‐di‐methoxytrityluridine 2 was converted to its 3′‐triflate 4 followed by derivatization to the respective N3‐t‐Boc product 5 . The triflate 5 was reacted with tetrabutylammonium[18F]fluoride to produce 6 , which by acid hydrolysis yielded compound 7 . The crude preparation was purified by HPLC to obtain the desired product [18F]‐FMXU. The radiochemical yields were 25–40% decay corrected (d. c.) with an average of 33% in four runs. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 67–75 min from the end of bombardment (EOB). Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
3.
Radiochemical synthesis of 2′‐[18F]‐labelled and 3′‐[18F]‐labelled nucleosides for positron emission tomography imaging
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Jan‐Philip Meyer Katrin C. Probst Andrew D. Westwell 《Journal of labelled compounds & radiopharmaceuticals》2014,57(5):333-337
This review article considers 2′‐labelled and 3′‐labelled nucleosides, which are of great importance as positron emission tomography (PET) probes in clinical diagnostics and PET research. Although the radiochemical preparation of several [18F]‐labelled nucleosides such as [18F]fluorothymidine or [18F](fluoroarabinofuranosyl)cytosine has been accomplished within the last two decades, a number of potentially interesting nucleoside‐based biomarkers are not yet available for automated good manufacturing practice production due to the lack of fast and efficient synthetic methods for late‐stage [18F]‐introduction. In order to meet recent demands for new PET‐based biomarkers in various clinical applications, appropriate precursors that can easily be fluorinated and deprotected need to be developed. 相似文献
4.
Andrew N. Gifford Caitlin V. Bennett Joanna S. Fowler 《Journal of labelled compounds & radiopharmaceuticals》2012,55(12):441-446
Fluorinated and deoxysucrose analogues have been proven useful in probing the substrate specificity and roles of sucrose processing enzymes and transporters in plants. To synthesize an 18F‐labeled fluorodeoxysucrose analogue suitable for in vivo studies, an acyl‐protected, disaccharide‐based radiofluorination precursor (sucrose 1′‐O‐trifluoromethanesulfonyl‐2,3,4,6,3′,4′,6′‐hepta‐O‐acetate; 2) was prepared by regioselective mono‐deacetylation of sucrose octaacetate using a commercial esterase enzyme followed by conversion of the resultant sucrose heptaacetate to the corresponding triflate. Reaction of this triflate precursor with [18F]fluoride followed by base hydrolysis to remove the acetate groups and HPLC purification gave 1′‐[18F]fluoro‐1′‐deoxysucrose (4) in an overall synthesis time of 80 min and with a median decay corrected yield of 26% (n = 4). This study demonstrates the use of an enzymatic approach to aid the synthesis of a regiospecific radiofluorination precursor starting from the readily available fully acetylated sugar, thus avoiding the need for a complex classical carbohydrate protection strategy to individually protect each hydroxyl group in the molecule. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
5.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(13):1181-1189
The use of the key enzyme involved in carbon–fluorine bond formation in Streptomyces cattleya catalysing the formation of 5′‐fluoro‐5′‐deoxyadenosine (5′‐FDA) from fluoride ion and S‐adenosyl‐l‐methionine (SAM) was explored for its potential application in fluorine‐18 labelling of the adenosine derivative. Enzymatic radiolabelling of [18F]‐5′‐FDA was successfully carried out starting from SAM and [18F]HF when the concentration of the enzyme preparation was increased from sub‐mg/ml values to mg/ml values. The purity of the enzyme had no measurable effect on the radiochemical yield of the reaction and the radiochemical purity of [18F]‐5′‐FDA. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
6.
Olaf Prante Kurt Hamacher Heinz H. Coenen 《Journal of labelled compounds & radiopharmaceuticals》2007,50(1):55-63
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 © 2007 John Wiley & Sons, Ltd. 相似文献
7.
William P. Tong Juri G. Gelovani Mian M. Alauddin 《Journal of labelled compounds & radiopharmaceuticals》2011,54(5):233-238
Introduction: The hepatocellular carcinoma–intestine–pancreas and pancreatitis‐associated proteins, also known as lactose‐binding protein, is upregulated in peritumoral pancreatic tissue. Previously, we reported ethyl‐ β ‐D ‐galactopyranosyl‐(1,4′)‐2′‐deoxy‐2′‐[18F]fluoro‐ β ‐D ‐glucopyranoside (Et‐[18F]‐FDL), a radiofluorinated lactose analog for positron emission tomography (PET) of small pancreatic carcinomas in mice. However, synthesis of the precursor for Et‐[18F]‐FDL involves 11 steps, which is quite lengthy, and produces overall low yields. Here, we report on synthesis and radiolabeling of another analog of lactose, the 1′‐[18F]fluoroethyl‐ β ‐D ‐lactose for PET imaging of pancreatic carcinomas. Methods: Two precursor compounds, 1′‐bromoethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐ β ‐D ‐lactose 4, and 1′‐p‐toluenesulfonylethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐ β ‐D ‐lactose 5, were synthesized in two and three steps, respectively; then, cold fluorination and radiofluorination of these precursors were performed. The reaction mixture was passed through a silica gel Sep‐pack cartridge, eluted with EtOAc, and the 1′‐[18F]fluoroethyl‐2′,3′,6′,2,3,4,6‐hepta‐O‐acetyl‐ β ‐D ‐lactose ([18F]‐6) purified by HPLC. After hydrolysis of the protecting groups, the 1′‐[18F]fluoroethyl‐ β ‐D ‐lactose [18F]‐7 was neutralized, diluted with saline, filtered through a sterile Millipore filter, and analyzed by radio‐TLC. Results: The average decay‐corrected radiochemical yield was 9% (n = 7) with>99% radiochemical purity and specific activity of 55.5 GBq/ µ mol. Conclusion : A new analog of lactose, 1′‐[18F]fluoroethyl‐ β ‐D ‐lactose, has been synthesized in good yields, with high purity and high specific activity suitable for PET imaging of early pancreatic carcinomas. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
8.
Timothy R. Neal William C. Schumann Marc S. Berridge Bernard R. Landau 《Journal of labelled compounds & radiopharmaceuticals》2005,48(11):845-854
With the goal of developing a PET radioligand for the in vivo assessment of glucose transport, 6-deoxy-6-[18F]fluoro-D -glucose ([18F]6FDG) was prepared in two steps from 18F−. Starting with D -glucose, the tosyl- and mesyl-derivatives of 3,5-O-benzylidene-1,2-O-isopropylidene-α-D -glucofuranose were prepared by known methods. Reaction of either of these precursors with 18F− resulted in the formation of 3,5-O-benzylidene-6-deoxy-6-[18F]-fluoro-1,2-O-isopropylidene-α-D -glucofuranose in high yield. Subsequent hydrolysis resulted in the production of [18F]6FDG. Under optimal conditions, [18F]6FDG is produced 60–70 min after end of bombardment (EOB) in 71 ± 12% yield (decay corrected, based upon fluoride) with a radiochemical purity of ⩾96%. Preliminary experiments have indicated that [18F]6FDG may be a more representative in vivo tracer for the glucose transporter than 2FDG. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
9.
Babak Behnam Azad Raman Chirakal Gary J. Schrobilgen 《Journal of labelled compounds & radiopharmaceuticals》2007,50(14):1236-1242
Previous work from this laboratory has shown that the direct fluorination of 3, 4‐dihydroxy‐phenyl‐L ‐alanine (L ‐DOPA) in anhydrous HF (aHF) or BF3/HF with F2 is an efficient method for the synthesis of 6‐fluoro‐L ‐DOPA. Since then, 18F‐labeled 6‐fluoro‐L ‐DOPA ([18F]6‐fluoro‐L ‐DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L ‐DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F]fluoro‐L ‐DOPA and [18F]fluoro‐D‐DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [18F]F2). The 2‐ and 6‐FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]‐FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
10.
11.
Vincenzo Paolillo Stefan Riese Juri G. Gelovani Mian M. Alauddin 《Journal of labelled compounds & radiopharmaceuticals》2009,52(13):553-558
2′‐Deoxy‐2′‐[18F]fluoro‐5‐substituted‐1‐β‐D ‐arabinofuranosyluracils, including 2′‐deoxy‐2′‐[18F]fluoro‐5‐methyl‐1‐β‐D ‐arabinofuranosyluracil [18F]FMAU and [18F]FEAU are established radiolabeled probes to monitor cellular proliferation and herpes simplex virus type 1 thymidine kinase (HSV1‐tk) reporter gene expression with positron emission tomography. For clinical applications, a fully automated CGMP‐compliant radiosynthesis is necessary for production of these probes. However, due to multiple steps in the synthesis, no such automated synthetic protocols have been developed. We report here a fully automated synthesis of [18F]‐FEAU and [18F]‐FMAU on a prototype dual reactor module TRACERlab FX FN. The synthesis was performed by using a computer‐programmed standard operating procedure, and the product was purified on a semipreparative high‐performance liquid chromatography (HPLC) integrated with the synthesis module using 12% EtOH in 50 mM Na2HPO4. Finally, the percentage of alcohol was adjusted to 7% by adding Na2HPO4 and filtered through a Millipore filter to make dose for human. The radiochemical yield on the fluorination was 40±10% (n=10), and the overall yields were 4±1% (d. c.), from the end of the bombardment; [18F]FEAU (n=7) and [18F]FMAU (n=3). The radiochemical purity was >99%, specific activity was 1200–1300 mCi/µmol. The synthesis time was 2.5 h. This automated synthesis should be suitable for production of [18F]FIAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and other 5‐substitued thymidine analogues. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
12.
Friederike Beyerlein Markus Piel Sabine Höhnemann Frank Rösch 《Journal of labelled compounds & radiopharmaceuticals》2013,56(7):360-363
Automated synthetic procedures of [18F]fluoro‐[di‐deutero]methyl tosylate on a GE TRACERlab FX F‐N module and a non‐commercial synthesis module have been developed. The syntheses included azeotropic drying of the [18F]fluoride, nucleophilic 18F‐fluorination of bis(tosyloxy)‐[di‐deutero]methane, HPLC purification and subsequent formulation of the synthesized [18F]fluoro‐[di‐deutero]methyl tosylate (d2‐[18F]FMT) in organic solvents. Automation shortened the total synthesis time to 50 min, resulting in an average radiochemical yield of about 50% and high radiochemical purity (>98%). The possible application of this procedure to commercially available synthesis modules might be of significance for the production of deuterated 18F‐fluoromethylated imaging probes in the future. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
13.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(6):463-471
A synthesis method has been developed for the labelling of N‐(3‐[18F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane ([18F]β‐CFT‐FP), a potential radioligand for visualization of the dopamine transporters by positron emission tomography. The two‐step synthesis includes preparation of [18F]fluoropropyl tosylate and its use without purification in the fluoroalkylation of 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane (nor‐β‐CFT). The final product is purified by HPLC. Optimization of the two synthesis steps resulted in a greater than 30% radiochemical yield of [18F]β‐CFT‐FP (decay corrected to end of bombardment). The synthesis time including HPLC‐purification was approximately 90 min. The radiochemical purity of the final product was higher than 99% and the specific radioactivity at the end of synthesis was typically 20 GBq/µmol. In comparison to alkylation by [18F]fluoropropyl bromide, the procedure described here results in an improved overall radiochemical yield of [18F]β‐CFT‐FP in a shorter time. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
14.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(9):745-755
Reductive coupling reactions between 4‐[18F]fluoro‐benzaldehyde ([18F] 1 ) and different alcohols by use of decaborane (B10H14) as reducing agent have the potential to synthesize 4‐[18F]fluoro‐benzylethers in one step. [18F] 1 was synthesized from 4‐trimethylammonium benzaldehyde (triflate salt) via a standard fluorination procedure (K[18F]F/Kryptofix® 222) in dimethylformamide at 90°C for 25 min and purified by solid‐phase extraction. Subsequently, reductive etherifications of [18F] 1 were performed as one‐step reactions with primary and secondary alcohols, mediated by B10H14 in acetonitrile at 60°C. Various 4‐[18F]fluorobenzyl ethers (6 examples are shown) were obtained within 1–2 h reaction time in decay‐corrected radiochemical yields of 12–45%. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
15.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(8):469-476
3‐[18F]Fluoropropyl‐, 4‐[18F]fluorobenzyl‐triphenylphosphonium and 4‐[18F]fluorobenzyltris‐4‐dimethylaminophenylphosphonium cations were synthesized in multi‐step reactions from no carrier added (nca) [18F]fluoride. The time for synthesis, purification, and formulation was 56, 82, and 79 min with an average radiochemical yield of 12, 6 and 15%, respectively (not corrected for decay). The average specific radioactivity for the three radiolabeled compounds was 14.9 GB q/µmole (403 mCi/µmole) at end of synthesis (EOS). Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
16.
Babak Behnam Azad Rezwan Ashique N. Renée Labiris Raman Chirakal 《Journal of labelled compounds & radiopharmaceuticals》2012,55(1):23-28
Fluorine‐18 labeled (2S,4S)‐4‐fluoro‐l ‐proline (cis‐[18F]4‐FPro) has been reported to be a potential positron emission tomography tracer to study abnormal collagen synthesis occurring in pulmonary fibrosis, osteosarcomas, mammary and colon carcinomas. In this paper, we report the stereospecific radiofluorination of (2S,4R)‐N‐tert‐butoxycarbonyl‐4‐(p‐toluenesulfonyloxy) proline methyl ester (at 110°C) to produce diastereomerically pure cis‐[18F]4‐FPro in 38% radiochemical yield at the end of a 90‐min synthesis. Investigation of the effect of temperature on the stereospecificity of nucleophilic fluorination showed that diasteriomerically pure cis‐[18F]4‐FPro or trans‐[18F]4‐FPro was produced at lower temperatures (85°C–110°C) during the fluorination of (2S,4R) or (2S,4S) precursors, respectively. However, at higher temperatures (130°C–145°C), fluorination of (2S,4R) precursor produced a mixture of cis‐[18F]4‐FPro and trans‐[18F]4‐FPro diastereomers with cis‐[18F]4‐FPro as the predominant isomer. Hydrolysis of the purified fluorinated intermediate was carried out either in one step, using 2 m triflic acid at 145°C for 10 min, or in two steps where the intermediate was heated in 1 m HCl at 110°C for 10 min followed by stirring at room temperature in 1 N NaOH for 5 min. The aqueous hydrolysis mixture was loaded onto an anion exchange column (acetate form for one‐step hydrolysis) or an ion retardation column (two‐step hydrolysis) followed by a C18 Sep‐Pak® (Waters Corporation, Milford, MA, USA). Pure cis‐[18F]4‐FPro was then eluted with sterile water. We also report that epimerization of cis‐[18F]4‐FPro occurs during the two‐step hydrolysis (H+ followed by OH?) of the intermediate, resulting in 5 ± 3% trans‐[18F]4‐FPro, whereas the one‐step acid hydrolysis yielded pure cis‐[18F]4‐FPro in the final product. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
17.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(7):653-661
The one step radiosynthesis of 2‐amino‐6‐ [18F]fluoro‐9‐(4‐hydroxy‐3‐hydroxymethylbutyl) purine (6‐[18F]fluoropenciclovir) 6 is reported. Radiolabeled product 6‐[18F]fluoropenciclovir 6 was prepared by radiofluorination of compound 4 with [18F]KF and isolated by a silica Sep‐Pak cartridge. The radiochemical yield of compound 6 was 45–55% decay corrected (d.c.) in six runs with radiochemical purity >98% and the radiosynthesis time was 35–42 min from end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
18.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(6):489-504
2‐exo‐(2′‐Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane (F2PhEP), a novel, epibatidine‐based, α4β2‐selective nicotinic acetylcholine receptor antagonist of low toxicity, as well as the corresponding N‐Boc‐protected chloro‐ and bromo derivatives as precursors for labelling with fluorine‐18 were synthesized from 7‐tert‐butoxycarbonyl‐7‐azabicyclo[2.2.1]hept‐2‐ene in 13, 19 and 8% overall yield, respectively. [18F]F2PhEP was prepared in 8–9% overall yield (non‐decay‐corrected) using 1 mg of the bromo derivative in the following two‐step radiochemical process: (1) no‐carrier‐added nucleophilic heteroaromatic ortho‐radiofluorination with the activated K[18F]F‐Kryptofix®222 complex in DMSO using microwave activation at 250 W for 90 s, followed by (2) quantitative TFA‐induced removal of the N‐Boc protective group. Radiochemically pure (>95%) [18F]F2PhEP (1.48–1.66 GBq, 74–148 GBq/µmol) was obtained after semi‐preparative HPLC (Symmetry® C18, eluent aqueous 0.05 M NaH2PO4 CH3CN: 78/22 (v:v)) in 75–80 min starting from an 18.5 GBq aliquot of a cyclotron‐produced [18F]fluoride production batch. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
19.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(11):1087-1092
Several [18F]‐labeled α‐trifluoromethyl ketones have been synthesized. Reactions of 2,2‐difluoro‐1‐aryl‐1‐trimethylsiloxyethenes ( 1a–d ) with [18F]‐F2 at low temperature produced [18F]‐labeled α‐trifluoromethyl ketones ( 2a–d ). Radio‐labeled products were isolated by purification with column chromatography in 22–28% yields, decay corrected (d.c.) in three runs per compound. Radiochemical purity was >99% with specific activities 15–20 GBq/mmol at the end of synthesis (EOS). The synthesis time was 35–40 min from the end of bombardment (EOB). This one‐step simple method is highly useful for the radiochemical synthesis of potential biologically active [18F]‐labeled α‐trifluoromethyl ketones for PET imaging. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
20.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(12):1093-1103
Labelled oligonucleotides are new imaging tools to study gene expression at the nucleic acid and protein levels. We have previously developed a universal method to label oligonucleotides at their 3′‐end with radiohalogens and particularly with fluorine‐18, the most widely used positron‐emitter, t1/2: 109.8 min. Using the same strategy, we herein report the fluorine‐18 labelling of oligonucleotides at their 5′‐end. A 18‐mer 2′O‐methyl modified oligoribonucleotide, bearing a phosphorothioate group at its 5′‐end, was conjugated to our fluorine‐18‐labelled reagent N‐(4‐[18F]fluorobenzyl)‐2‐bromoacetamide. The whole synthetic procedure yielded up to 1 GBq of fluorine‐18‐labelled oligonucleotide with a specific radioactivity of 37–74 GBq/μmol in 160 min. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献