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1.
Patrick J. Riss Sabine Hoehnemann Markus Piel Frank Roesch 《Journal of labelled compounds & radiopharmaceuticals》2013,56(7):356-359
The cocaine‐derived dopamine reuptake inhibitors FE‐β‐CIT (8‐(2‐fluoroethyl)‐3‐(4‐iodophenyl)‐8‐azabicyclo[3.2.1]octane‐2‐carboxylic acid methyl ester) (1) and PR04.MZ(8‐(4‐fluorobut‐2‐ynyl)‐3‐p‐tolyl‐8‐azabicyclo[3.2.1]octane‐2‐carboxylic acid methyl ester) (2) were labelled with 18F‐fluorine using a two‐step route. 2‐[18F]Fluoroethyltosylate and 4‐[18F]fluorobut‐2‐yne‐1‐yl tosylate were used as labelling reagents, respectively. Radiochemically pure (>98%) [18F]FE‐β‐CIT and [18F]PRD04.MZ (32–86 GBq/µmol) were obtained after a synthesis time of 100 min in about 25% non‐decay‐corrected overall yield. 相似文献
2.
Ofer Shamni Bruno Nebeling Hilbert Grievink Eyal Mishani 《Journal of labelled compounds & radiopharmaceuticals》2019,62(6):252-258
Radiolabeled prostate‐specific membrane antigen (PSMA) targeting PET‐tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [18F]PSMA‐1007 was introduced as an alternative to [68Ga]Ga‐PSMA‐11, for staging and diagnosing biochemically recurrent PC. We incorporated a one‐step procedure for [18F]PSMA‐1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure. Although the adapted [18F]PSMA‐1007 synthesis resulted in repeatable radiochemical yields (55 ± 5%, NDC), suboptimal radiochemical purities of 87 ± 8% were obtained using both modules. As described here, modifications made to the radiolabeling and the solid‐phase extraction purification steps reduced synthesis time to 32 minutes and improved radiochemical purity to 96.10%, using both modules, without shearing the radiochemical yield. 相似文献
3.
《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
4.
Nashaat Turkman Juri G. Gelovani Mian M. Alauddin 《Journal of labelled compounds & radiopharmaceuticals》2010,53(13):782-786
Direct fluorination of a pyrimidine nucleoside at the 2′‐arabino‐position has been deemed to be extremely difficult, if not impossible. The conventional synthesis of 2′‐deoxy‐2′‐fluoro‐5‐methy‐1‐β‐D ‐arabinofuranosyluracil (FMAU) and its 5‐substituted analogs involves stereospecific fluorination of the 1,3,5‐tri‐O‐benzoyl‐α‐D ‐ribofuranose‐2‐sulfonate ester followed by bromination at the C1‐postion, and then coupling with pyrimidine‐bis‐trimethylsilyl ether. Several radiolabeled nucleoside analogs, including [18F]FMAU, and other 5‐substituted analogs, were developed according to this methodology. However, routine production of these compounds using this multi‐step process is inconvenient and limits their clinical application. We developed a novel precursor and method for direct fluorination of preformed nucleoside analogs at the 2′‐arabino position, exemplified via radiosynthesis of [18F]FMAU. The 2′‐methylsulfonyl‐3′,5′‐O‐tetrahydropyranyl‐N3‐Boc‐5‐methyl‐1‐β‐D ‐ribofuranosiluracil was synthesized in multiple steps. Radiofluorination of this precursor with K18F/kryptofix produced 2′‐deoxy‐2′‐[18F]fluoro‐3′,5′‐O‐tetrahydropyranyl‐N3‐Boc‐5‐methyl‐1‐β‐D ‐arabinofuranosiluracil. Acid hydrolysis followed by high‐performance liquid chromatography purification produced the desired [18F]FMAU. The average radiochemical yield was 2.0% (decay corrected, n=6), from the end of bombardment. Radiochemical purity was >99%, and specific activity was >1800 mCi/µmol. Synthesis time was 95–100 min from the end of bombardment. This direct fluorination is a novel method for synthesis of [18F]FMAU, and the method should be suitable for production of other 5‐substituted pyrimidine analogs, including [18F]FEAU, [18F]FIAU, [18F]FFAU, [18F]FCAU, and [18F]FBAU. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
5.
《Journal of labelled compounds & radiopharmaceuticals》2017,60(2):140-146
The radiotracer, [18F]‐THK‐5351, is a highly selective and high‐binding affinity PET imaging agent for aggregates of hyper‐phosphorylated tau protein. Our report is a simplified 1‐pot, 2‐step radiosynthesis of [18F]‐THK‐5351. This report is broadly applicable for routine clinical production and multi‐center trials on account of favorable half‐life of flourine‐18 and the use of a commercially available radiosynthesis module, the GE TRACERlab™ FXFN. First, the O‐THP protected tosyl precursor underwent nucleophilic fluorinating reaction with potassium cryptand fluoride ([18F] fluoride (K[18F]/K222)) in Dimethyl sulfoxide at 110°C for 10 minutes followed by O‐THP removal by using diluted hydrochloric acid (HCl) at same temperature. [18F]‐THK‐5351 was purified via semi‐preparative high‐performance liquid chromatography and formulated by using 10% EtOH, United States Pharmacopeia (USP) in 0.9% sodium chloride for injection, USP and an uncorrected radiochemical yield of 21 ± 3.5%, with a specific activity of 153.11 ± 25.9 GBq/μmol (4138 ± 700 mCi/μmol) at the end of synthesis (63 minutes; n = 3). 相似文献
6.
《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
7.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(9):805-814
The syntheses of adenosine analogues, 2′‐deoxy‐2′‐[18F]fluoro‐9‐β‐D ‐arabinofuranosyladenine ([18F]‐FAA) and 3′‐deoxy‐3′‐[18F]fluoro‐9‐β‐D ‐xylofuranosyladenine ([18F]‐FXA) are reported. Adenosine ( 1 ) was converted to its methoxytrityl derivatives 2 and 3 as a mixture. After separation, these derivatives were converted to their respective triflates 4 and 5 . Each triflate was reacted with tetrabutylammonium[18F]fluoride to produce 6b or 7b , which by acidic hydrolysis yielded compounds 8b and 9b . Crude preparations were purified by HPLC to obtain the desired pure products. The radiochemical yields were 10‐18% decay corrected (d. c.) for 8b and 30‐40% (d. c.) for 9b in 4 and 3 runs, respectively. Radiochemical purity was >99% and specific activity was >74 GBq/μmol at the end of synthesis (EOS). The synthesis time was 90‐95 min from the end of bombardment (EOB). Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
8.
Matthias Glaser Erik Årstad Sajinder K. Luthra Edward G. Robins 《Journal of labelled compounds & radiopharmaceuticals》2009,52(8):327-330
The acylation reagent [18F]N‐succinimidyl‐4‐fluorobenzoate (18F‐SFB) has been prepared using a new two‐step approach. The starting material p‐[18F]fluorobenzaldehyde (18F‐FBA) was obtained by an improved radiosynthesis with a decay‐corrected radiochemical yield of 66±6 % (n=3). Reaction of 18F‐FBA with (diacetoxyiodine)benzene and N‐hydroxysuccinimide and preparative HPLC purification furnished 18F‐SFB in an r.c.y. of 49±6 % (n=3), based on the starting radioactivity of 18F‐FBA. The radiochemical purity of 18F‐SFB was >99%. Alternatively, purification by solid phase extraction gave 18F‐SFB with an r.c.y. of 77±9% (n=4) and a radiochemical purity of 89±5% (n=4). This radiochemical synthesis only used non‐aqueous solvents, which simplifies the method and facilitates subsequent applications of 18F‐SFB. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
9.
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
10.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(4):285-289
Several 2′‐deoxy‐2′‐[18F]fluoro‐1‐β‐D‐arabinofuranosyluracil derivatives have been synthesized. Coupling of 1‐bromo‐2‐deoxy‐2‐[18F]fluoro‐3,5‐di‐O‐benzoyl‐α‐D‐arabinofuranose 2 with protected uracil derivatives 3a–e followed by hydrolysis and high‐performance liquid chromatography purification produced the radiolabeled nucleosides 4a–e in 15–30% yield (d. c.), >99% radiochemical purity and 55.5–103.6 GBq/µmol specific activities. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
11.
Xia Shao Raphaël Hoareau Brian G. Hockley Louis J. M. Tluczek Bradford D. Henderson Henry C. Padgett Peter J. H. Scott 《Journal of labelled compounds & radiopharmaceuticals》2011,54(6):292-307
The field of radiochemistry is moving toward exclusive use of automated synthesis modules for production of clinical radiopharmaceutical doses. Such a move comes with many advantages, but also presents radiochemists with the challenge of re‐configuring synthesis modules for production of radiopharmaceuticals that require nonconventional radiochemistry while maintaining full automation. This review showcases the versatility of the Tracerlab FXFN synthesis module by presenting simple, fully automated methods for producing [18F]FLT, [18F]FAZA, [18F]MPPF, [18F]FEOBV, [18F]sodium fluoride, [18F]fluorocholine and [18F]SFB. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
12.
Ganghua Tang Xiaolan Tang Mingfang Wang Baoyuan Li Mingquan Liang Quanshi Wang 《Journal of labelled compounds & radiopharmaceuticals》2008,51(7):297-301
Two fully automated synthetic procedures of [18F]fluoroacetate ([18F]FAC) have been developed using a modified commercial TRACERlab FXFN synthesizer. One was a two‐step one‐pot procedure, consisting of nucleophilic [18F]fluorination of benzyl‐2‐bromoacetate as a precursor with no‐carrier‐added [18F]fluoride, hydrolysis within the same [18F]fluorination reaction vessel, and purification with/without high‐performance liquid chromatography (HPLC). The second procedure consisted of nucleophilic [18F]fluorination, hydrolysis on the column, and purification with SEP‐PAK cartridges instead of HPLC. The radiochemical purity of [18F]FAC was >95% by the two procedures. The second procedure was a simple, rapid, and fully automated synthesis of [18F]FAC with a high and reproducible radiochemical yield exceeding 60% (decay uncorrected) within the total synthesis time less than 20 min. The new, simple, and rapid on‐column hydrolysis procedure should be adaptable to the fully automated synthesis of [18F]FAC at a commercial fluoro‐deoxyglucose synthesis module. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
13.
Ken Kersemans John Mertens Vicky Caveliers 《Journal of labelled compounds & radiopharmaceuticals》2010,53(2):58-62
Currently there is still a need for more potent amino acid analogues as tumour imaging agents for peripheral tumour imaging with PET as it was recently reported that the success of O‐(2′‐[18F]fluoroethyl)‐L ‐tyrosine ([18F]FET) is limited to brain, head and neck tumours. As the earlier described 2‐Amino‐3‐(2‐[18F]fluoromethyl‐phenyl)‐propionic acid (2‐[18F]FMP) suffered from intramolecular‐catalysed defluorination, we synthesized 2‐Amino‐3‐(4‐[18F]fluoromethyl‐phenyl)‐propionic acid (4‐[18F]FMP) as an alternative for tumour imaging with PET. Radiosynthesis of 4‐[18F]FMP, based on Br for [18F] aliphatic nucleophilic exchange, was performed with a customized modular Scintomics automatic synthesis hotboxthree system in a high overall yield of 30% and with a radiochemical purity of \gt 99%. 4‐[18F]FMP was found to be stable in its radiopharmaceutical formulation, even at high radioactivity concentrations. Additionally, for a comparative study, [18F]FET was synthesized using the same setup in 40% overall yield, with a radiochemical purity \gt 99%. The described automated radiosynthesis allows the production of two different amino acid analogues with minor alternations to the parameter settings of the automated system, rendering this unit versatile for both research and clinical practice. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
14.
Ingrid Koslowsky Soraya Shahhosseini John Wilson John Mercer 《Journal of labelled compounds & radiopharmaceuticals》2008,51(10):352-356
The potential for radiolabeled antisense oligonucleotides to image gene expression combined with the enhanced resolution of positron‐emission tomography justifies the continued interest in the development of oligonucleotides tagged with positron‐emitting radionuclides. The radiolabeling of oligonucleotides is a multi‐step process and may require handling large amounts of radioactivity initially. A previously reported method for radiolabeling oligonucleotides with N‐(4‐[18F]fluorobenzyl)‐2‐bromoacetamide was adapted for use in a commercially available automated synthesis unit by linking two reaction trains. The yield of N‐(4‐[18F]fluorobenzyl)‐2‐bromoacetamide ranged from 3 to 18% and the synthesis was completed within 1 h. Challenges in using this unit included the maintenance of anhydrous conditions for the effective reduction of 4‐[18F]fluorobenzonitrile. Preliminary results indicated that a mean yield of 36% could be obtained upon incubation of an oligonucleotide with N–(4‐[18F]fluorobenzyl)‐2‐bromoacetamide. The entire synthesis could be performed within 3 h. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
15.
Timothy M. Shoup Daniel L. Yokell Peter A. Rice Raul N. Jackson Eli Livni Keith A. Johnson Thomas J. Brady Neil Vasdev 《Journal of labelled compounds & radiopharmaceuticals》2013,56(14):736-740
Fluorine‐18 labeled 7‐(6‐fluoropyridin‐3‐yl)‐5H‐pyrido[4,3‐b]indole ([18F]T807) is a potent and selective agent for imaging paired helical filaments of tau and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one‐step method for the synthesis of [18F]T807 that is broadly applicable for routine clinical production using a GE TRACERlab? FXFN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert‐butyl 7‐(6‐nitropyridin‐3‐yl)‐5H‐pyrido[4,3‐b]indole‐5‐carboxylate, as well as new HPLC separation conditions that enable a facile one‐step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [18F]fluoride (K[18F]/K222) in DMSO at 130 °C over 10 min the precursor is concurrently deprotected. Formulated [18F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/µmol (5837 ± 1621 mCi/µmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [18F]T807. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
16.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(12):1079-1088
Syntheses of N‐3(substituted) analogues of thymidine, N‐3([18F]fluorobutyl)thymidine ([18F]‐FBT) and N‐3([18F]fluoropentyl)thymidine ([18F]‐FPT) are reported. 1,4‐Butane diol and 1,5 pentane diol were converted to their tosyl derivatives 2 and 3 followed by conversion to benzoate esters 4 and 5, respectively. Protected thymidine 1 was coupled separately with 4 and 5 to produce 6 and 7 , which were hydrolyzed to 8 and 9 , then converted to their mesylates 10 and 11 , respectively. Compounds 10 and 11 were fluorinated with n‐Bu4N[18F] to produce 12 and 13 , which by acid hydrolysis yielded 14 and 15 , respectively. The crude products were purified by HPLC to obtain [18F]‐FBT and [18F]‐FPT. The radiochemical yields were 58–65% decay corrected (d.c.) for 14 and 46–57% (d.c.) for 15 with an average of 56% in three runs per compound. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 65–75 min from the end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
17.
Pradip Ghosh Juri G. Gelovani Mian M. Alauddin 《Journal of labelled compounds & radiopharmaceuticals》2007,50(13):1185-1191
Radiosyntheses of two N3‐substituted thymidine analogues, N3‐[(4[18F]fluoromethyl‐phenyl)butyl]thymidine ([18F]‐FMPBT) and N3‐[(4[18F]fluoromethyl‐phenyl)pentyl]thymidine ([18F]‐FMPPT), are reported. The precursor compounds 9 and 10 were synthesized in six steps and the standard compounds 13 and 14 were synthesized from these precursors. For radiosynthesis, compounds 9 and 10 were fluorinated with n‐Bu4N[18F] to produce [18F]‐ 11 and [18F]‐ 12 , which by acid hydrolysis yielded [18F]‐ 13 and [18F]‐ 14 , respectively. The crude products were purified by high‐performance liquid chromatography to obtain [18F]‐FMPBT and [18F]‐FMPPT. The average decay‐corrected radiochemical yield for [18F]‐ 13 was 15% in five runs, and that for [18F]‐ 14 was 10% in four runs. The radiochemical purity was >99% and the specific activity was >74 GBq/µmol at the end of synthesis. The synthesis time was 80–90 min from the end of bombardment. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
18.
Hayden T. Ravert Daniel P. Holt Robert F. Dannals 《Journal of labelled compounds & radiopharmaceuticals》2014,57(12):695-698
The 4‐[18F]‐fluorobenzyltriphenylphosphonium cation was synthesized by a series of microwave reactions from no carrier added [18F]‐fluoride. The microwave procedure reduced the quantity of reagents used and synthesis time when compared with the original synthesis. In addition, problematic solid phase extraction, sodium borohydride reduction by column and inconsistent yields with excessive precipitate formation during the bromination step were eliminated. The 4‐[18F]‐fluorobenzyltriphenylphosphonium cation was produced radiochemically pure in 8.3% yield with a specific radioactivity of 534.5 ± 371.4 GBq/µmole at end of synthesis. 相似文献
19.
Matthias Glaser Erik Årstad Alessandra Gaeta James Nairne William Trigg Edward G. Robins 《Journal of labelled compounds & radiopharmaceuticals》2012,55(9):326-331
18F‐labelled fluoroalkylamines are attractive reagents for the preparation of positron emission tomography tracers containing amine, amide, and N‐heterocyclic moieties. Herein, we report that 2‐[18F]fluoroethylamine can be obtained from 2‐[18F]fluoroethyl azide by reduction with elemental copper under acidic conditions. Azide to amine reduction was achieved in near quantitative analytical yields within 30 min by heating a solution of 2‐[18F]fluoroethyl azide in the presence of copper wire and aqueous trifluoroacetic acid. Subsequent reaction of 2‐[18F]fluoroethylamine with benzoyl chloride in the presence of triethylamine provided N‐[18F]fluoroethyl benzamide in 63% decay‐corrected radiochemical yield from 2‐[18F]fluoroethyl azide. The utility of the Cu(0)/H+ azide reduction method was further exemplified by preparation of the potential GABAA tracer 9H‐β‐carboline N‐2‐[18F]fluoroethylamide, which was obtained in 46% decay‐corrected radiochemical yield by reaction of 2‐[18F]fluoroethylamine with the corresponding 9H‐β‐carboline pentafluorophenyl ester. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
20.
Keith Graham Andre Müller Lutz Lehmann Norman Koglin Ludger Dinkelborg Holger Siebeneicher 《Journal of labelled compounds & radiopharmaceuticals》2014,57(3):164-171
The radiosynthesis of [18F]fluoropyruvate was investigated using numerous precursors were synthesized from ethyl 2,2‐diethoxy‐3‐hydroxypropanoate (5) containing different leaving groups: mesylate, tosylate, triflate, and nonaflate. These precursors were evaluated for [18F]fluoride incorporation with triflate being superior. The subsequent hydrolysis step was investigated, and an acidic hydrolysis was optimized. After establishing suitable purification and formulation methods, the [18F]fluoropyruvate could be isolated in ca. 50% d.c. yield. The [18F]fluoropyruvate was evaluated in vitro for its uptake into tumor cells using adenocarcinomic human alveolar basal epithelial cells (A549) and unfortunately showed an uptake of approximately 0.1% of the applied dose per 100,000 cells after 30 min. Initial pharmacokinetic properties were assessed in vivo using nude mice showed a high degree of bone uptake from defluorination, which will limit its potential as an imaging agent for metabolic processes. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献