共查询到20条相似文献,搜索用时 15 毫秒
1.
Ute Mühlhausen Johannes Ermert Heinz H. Coenen 《Journal of labelled compounds & radiopharmaceuticals》2009,52(1):13-22
In psychiatric disorders such as anxiety, depression and schizophrenia, 5‐HT2A receptors play an important role. In order to investigate them in vivo there is an increasing interest in selective and high‐affinity radioligands for receptor binding studies using positron emission tomography (PET). Since available radioligands have disadvantages, R91150, which is a selective and high‐affinity ligand for 5‐HT2A receptors, was labelled with fluorine‐18. This was accomplished in six steps via 4‐[18F]fluorophenol and 1‐(3‐bromopropoxy)‐4‐[18F]fluorobenzene within 190 min starting from no‐carrier‐added [18F]fluoride. The overall radiochemical yield was 3.8±2% and the specific activity was at least 335 GBq/µmol at the end of the synthesis. First ex vivo studies in mice proved the uptake of [18F]R91150 in the brain. Radiometabolite studies revealed no radiometabolites in the brain, whereas in the plasma at least two could be detected 30 min p.i. Further preclinical studies are encouraged to evaluate the potential of this new 5‐HT2A ligand as a radiotracer for PET. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
2.
Matthias M. Herth Vasko Kramer Nic Gillings Frank Rösch Gitte M. Knudsen 《Journal of labelled compounds & radiopharmaceuticals》2012,55(9):354-358
Imaging the serotonin 2A neuroreceptor with positron emission tomography has been carried out with [11C]MDL 100907 and [18F]altanserin for years. Recently, the MDL 100907 analogue [18F]MH.MZ was developed by combining the increased selectivity profile of MDL 100907 and the favourable radiophysical properties of fluorine‐18. Here, we want to report the synthesis of [18F]MH.MZ via direct radiofluorination. Unfortunately, the direct radiofluorination did not have any significant benefits over the indirect labelling method. This is mainly because the precursor for the direct labelling approach is not completely stable and slowly decomposes. However, only one HPLC separation is necessary for the direct 18F‐nucleophilic labelling procedure, and accordingly, automation is easier. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
3.
《Journal of labelled compounds & radiopharmaceuticals》2017,60(12):586-591
An agonist PET tracer is of key interest for the imaging of the 5‐HT2A receptor, as exemplified by the previously reported success of [11C]Cimbi‐36. Fluorine‐18 holds several advantages over carbon‐11, making it the radionuclide of choice for clinical purposes. In this respect, an 18F‐labelled agonist 5‐HT2A receptor (5‐HT2AR) tracer is highly sought after. Herein, we report a 2‐step, 1‐pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5‐HT2AR. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs. PET images partially conformed to the expected brain distribution of the 5‐HT2AR; a notable exception however being significant uptake in the striatum and thalamus. Additionally, a within‐scan displacement challenge with a 5‐HT2AR antagonist was unsuccessful, indicating that the tracers cannot be considered optimal for neuroimaging of the 5‐HT2AR. 相似文献
4.
Matthias M. Herth Vasko Kramer Frank Rösch 《Journal of labelled compounds & radiopharmaceuticals》2009,52(6):201-207
5‐HT1A receptors are involved in a variety of psychiatric disorders and in vivo molecular imaging of the 5‐HT1A status represents an important approach to analyze and treat these disorders. We report herein the synthesis of three new fluoroethylated 5‐HT1A ligands (AH1.MZ, AH2.MZ and AH3.MZ) as arylpiperazine derivatives containing a norbornene group. AH1.MZ (Ki= 4.2 nM) and AH2.MZ (Ki=30 nM) showed reasonable in vitro affinities to the 5‐HT1A receptor, whereas AH3.MZ appeared to be non‐affine toward the 5‐HT1A receptor. The receptor profile of AH1.MZ and AH2.MZ showed selectivity within the 5‐HT system. 18F‐labelling via [18F]FETos to [18F]AH1.MZ was carried out in radiochemical yields of >70%. The final formulation of injectable solutions including [18F]FETos synthon synthesis, radiosynthesis and semi‐preparative high‐performance liquid chromatography (HPLC) separation took no longer than 130 min and provided [18F]AH1.MZ with a purity of >98% as indicated by analytical HPLC analyses. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
5.
Matthias M. Herth Gitte M. Knudsen 《Journal of labelled compounds & radiopharmaceuticals》2015,58(7):265-273
Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been made to develop a suitable 5‐HT2AR positron emission tomography‐tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5‐HT2AR radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning outcomes that can be made from these tracer development processes. 相似文献
6.
Mohammad B. Haskali Peter D. Roselt John A. Karas Wayne Noonan Christian W. Wichmann Andrew Katsifis Rodney J. Hicks Craig A. Hutton 《Journal of labelled compounds & radiopharmaceuticals》2013,56(14):726-730
The versatile 18F‐labeled prosthetic group, 4‐nitrophenyl 2‐[18F]fluoropropionate ([18F]NFP), was synthesized in a single step in 45 min from 4‐nitrophenyl 2‐bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [18F]NFP, [18F]GalactoRGD — the current ‘gold standard’ tracer for imaging the expression of αVβ3 integrin — was prepared with high specific activity in 90 min and 20% decay corrected radiochemical yield from [18F]fluoride. 相似文献
7.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(7):443-455
The availability of no‐carrier‐added (n.c.a.) 4‐[18F]fluorophenol offers the possibility of introducing the 4‐[18F]fluorophenoxy moiety into potential radiopharmaceuticals. Besides alkyl–aryl ether synthesis using n.c.a. 4‐[18F]fluorophenol the diaryl ether coupling is an attractive synthetic method to enlarge the spectrum of interesting labelling procedures. As examples the syntheses of n.c.a. 2‐(4‐[18F]fluorophenoxy)‐N,N‐dimethylbenzylamine and n.c.a. 2‐(4‐[18F]fluorophenoxy)‐N‐methylbenzylamine were realized by an Ullmann ether synthesis of corresponding 2‐bromobenzoic acid amides using tetrakis(acetonitrile)copper(I) hexafluorophosphate as catalyst and a subsequent reduction of the amides formed. The radiochemical yield of the coupling varied between 5 and 65% based on labelled 4‐[18F]fluorophenol. Both compounds are structural analogues of recently published radiotracers for imaging the serotonin reuptake transporter sites (SERT). However, in vitro binding assays of both molecules showed only a low affinity towards monoamine transporters. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
8.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(9):811-815
2‐[18F]fluoroadenosine (2‐[18F]FAD), a potential radioligand for assessment of adenylate metabolism, was synthesized by carrier‐added and no‐carrier‐added procedures via nucleophilic radiofluorination of 2‐fluoroadenosine and 2‐iodoadenosine. The radiochemical yield, specific radioactivity and radiochemical purity of carrier‐added and no‐carrier‐added 2‐[18F]FAD were 5%, 22–30 mCi/µmol and 99%, and 0.5%, 1200–1700 mCi/µmol and 99%, respectively. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
9.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(9):531-542
4‐Fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide is a full 5‐HT1A agonist with high affinity (pKi=9.3), selectivity and a c log P of 3.045. The corresponding PET radioligand 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide was synthesized by nucleophilic aromatic substitution on the nitro precursor. The fluorinating agent K[18F]F/Kryptofix 2.2.2 was both dried (9 min, 700 W) and incorporated in the precursor (5 min, 700 W) using a commercially available microwave oven. In a total synthesis time of 60 min, an overall radiochemical yield of 18% (SD=5, n=7, EOS) was obtained. Radiochemical purity was always higher than 99% and specific activity always higher than 81.4 GBq/µmol (2.2 Ci/µmol). Initial brain uptake in mice was 2.19% ID (5.47% ID/g, 2 min) but decreased rapidly (0.17% ID, 0.45% ID/g (60 min)). During the first 20 min p.i., radioactivity concentration of the brain was significantly higher than that of blood demonstrating good brain entry of the tracer. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
10.
Kazutaka Hayashi Kenji Furutsuka Takehito Ito Masatoshi Muto Hatsumi Aki Toshimitsu Fukumura Kazutoshi Suzuki 《Journal of labelled compounds & radiopharmaceuticals》2012,55(3):120-124
We have developed an efficient synthesis method for the rapid and high‐yield automated synthesis of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[18F]fluorobenzamido]ethylpiperazine (p‐[18F]MPPF). No‐carrier‐added [18F]F? was trapped on a small QMA cartridge and eluted with 70% MeCN(aq) (0.4 mL) containing Kryptofix 222 (2.3 mg) and K2CO3 (0.7 mg). The nucleophilic [18F]fluorination was performed with 3 mg of the nitro‐precursor in DMSO (0.4 mL) at 190 °C for 20 min, followed by the preparative HPLC purification (column: COSMOSIL Cholester, Nacalai Tesque, Kyoto, Japan; mobile phase: MeCN/25 mm AcONH4/AcOH = 200/300/0.15; flow rate: 6.0 mL/min) to afford p‐[18F]MPPF (retention time = 9.5 min). p‐[18F]MPPF was obtained automatically with a radiochemical yield of 38.6 ± 5.0% (decay corrected, n = 5), a specific activity of 214.3 ± 21.1 GBq/µmol, and a radiochemical purity of >99% within a total synthesis time of about 55 min. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
11.
Brian G. Hockley Megan N. Stewart Phillip Sherman Carole Quesada Michael R. Kilbourn Roger L. Albin Peter J. H. Scott 《Journal of labelled compounds & radiopharmaceuticals》2013,56(12):595-599
(?)‐[18F]Flubatine was selected for clinical imaging of α4β2 nicotinic acetylcholine receptors because of its high affinity and appropriate kinetic profile. A fully automated synthesis of (?)‐[18F]flubatine as a sterile isotonic solution suitable for clinical use is reported, as well as the first evaluation in nonhuman primates (rhesus macaques). (?)‐[18F]Flubatine was prepared by fluorination of the Boc‐protected trimethylammonium iodide precursor with [18F]fluoride in an automated synthesis module. Subsequent deprotection of the Boc group with 1‐M HCl yielded (?)‐[18F]flubatine, which was purified by semi‐preparative HPLC. (?)‐[18F]Flubatine was prepared in 25% radiochemical yield (formulated for clinical use at end of synthesis, n = 3), >95% radiochemical purity, and specific activity = 4647 Ci/mmol (171.9 GBq/µmol). Doses met all quality control criteria confirming their suitability for clinical use. Evaluation of (?)‐[18F]flubatine in rhesus macaques was performed with a Concorde MicroPET P4 scanner (Concorde MicroSystems, Knoxville, TN). The brain was imaged for 90 min, and data were reconstructed using the 3‐D maximum a posteriori algorithm. Image analysis revealed higher uptake and slower washout in the thalamus than those in other areas of the brain and peak uptake at 45 min. Injection of 2.5 µg/kg of nifene at 60 min initiated a slow washout of [18F]flubatine, with about 25% clearance from the thalamus by the end of imaging at 90 min. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
12.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(7):429-441
The availability of no‐carrier‐added (n.c.a.) 1‐bromo‐4‐[18F]fluorobenzene with high radiochemical yields is important for 18F‐arylation reactions using metallo‐organic 4‐[18F]fluorophenyl compounds (e.g. of lithium or magnesium) or Pd‐catalyzed coupling. In this study, different methods for the preparation of 1‐bromo‐4‐[18F]fluorobenzene by nucleophilic aromatic substitution reactions using n.c.a. [18F]fluoride were examined. Of six pathways compared, symmetrical bis‐(4‐bromphenyl)iodonium bromide proved most useful to achieve the title compound in a direct, one‐step nucleophilic substitution with a radiochemical yield (RCY) of 65% within 10 min. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
13.
Thomas Bourdier Christopher J. R. Fookes Tien Q. Pham Ivan Greguric Andrew Katsifis 《Journal of labelled compounds & radiopharmaceuticals》2008,51(11):369-373
The F‐18 labelled methionine derivative S‐(2‐[18F]fluoroethyl)‐L‐homocysteine ([18F]FEHCys) was prepared by a one‐pot two‐step synthesis via the protected S‐(2‐bromoethyl)‐L‐homocysteine 1 and S‐(2‐chloroethyl)‐L‐homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro‐analogue (22% at 100°C in 30 min). However, [18F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
14.
Automated cGMP‐compliant radiosynthesis of [18F]‐(E)‐PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5
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Jun Young Park Jeongmin Son Mijin Yun Simon M. Ametamey Joong‐Hyun Chun 《Journal of labelled compounds & radiopharmaceuticals》2018,61(1):30-37
(E)‐3‐(Pyridin‐2‐yl ethynyl)cyclohex‐2‐enone O‐(3‐(2‐[18F]‐fluoroethoxy)propyl) oxime ([18F]‐(E)‐PSS232, [18F] 2a ) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu5) in vivo. The mGlu5 has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon‐11‐labeled and fluorine‐18‐labeled radiotracers have been developed to measure mGlu5 receptor occupancy in the human brain. The radiotracer [18F] 2a , which is used as an analogue for [11C]ABP688 ([11C] 1 ) and has a longer physical half‐life, is a selective radiotracer that exhibits high binding affinity for mGlu5. Herein, we report the fully automated radiosynthesis of [18F] 2a using a commercial GE TRACERlab? FX‐FN synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron‐produced [18F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high‐performance liquid chromatography (HPLC) purification and formulation, readily provided [18F] 2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [18F]‐(E)‐conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 minutes. 相似文献
15.
《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
16.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(1):31-43
The palladium‐mediated N‐arylation of indoles with 4‐[18F]fluoroiodobenzene as a novel radiolabelling method has been developed. Optimized reaction conditions were elaborated by variation of different catalyst systems (CuI/1,2‐diamines and Pd2(dba)3/phosphine ligands), bases and solvents in the reaction of indole with 4‐[18F]fluoroiodobenzene. Optimized reaction conditions (Pd2(dba)3/(2‐(dicyclohexyl‐phosphino)‐2′‐(N,N‐dimethylamino)‐biphenyl, NaOBut, toluene, 100°C for 20 min) were applied for the synthesis of 18F‐labelled σ2 receptor ligands [18F]‐11 and [18F]‐13 which were obtained in 91 and 84% radiochemical yields, respectively. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
17.
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
18.
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
19.
Automated production at the curie level of no‐carrier‐added 6‐[18F]fluoro‐ l‐dopa and 2‐[18F]fluoro‐ l‐tyrosine on a FASTlab synthesizer
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C. Lemaire L. Libert X. Franci J.‐L. Genon S. Kuci F. Giacomelli A. Luxen 《Journal of labelled compounds & radiopharmaceuticals》2015,58(7):281-290
An efficient, fully automated, enantioselective multi‐step synthesis of no‐carrier‐added (nca) 6‐[18F]fluoro‐L‐dopa ([18F]FDOPA) and 2‐[18F]fluoro‐L‐tyrosine ([18F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high‐ performance liquid chromatography (HPLC) purification has been developed. A PTC (phase‐transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand‐alone HPLC. [18F]FDOPA and [18F]FTYR were produced in 36.3 ± 3.0 % (n = 8) and 50.5 ± 2.7 % (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95 %, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [18F]FDOPA and [18F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment. 相似文献
20.
P. Blanckaert I. Burvenich F. Devos G. Slegers 《Journal of labelled compounds & radiopharmaceuticals》2007,50(3):183-188
This work reports the synthesis, radiolabelling and in vivo evaluation in NMRI mice of [123I]‐(4‐fluorophenyl)[1‐(3‐iodophenethyl)piperidin‐4‐yl]methanone ([123I]‐3‐I‐CO) as a potential SPECT tracer for the 5‐HT2A receptor. The tributylstannylprecursor was synthesized with a 15% overall yield. Radiolabelling was performed using an electrophilic iododestannylation with yields of 85%. Radiochemical purity was always >95%. Log P was determined to be 3.10±0.10. The tracer showed good uptake in mouse brain (6.3±1.3% ID/g tissue at 10 min p.i., 2±0.36% ID/g tissue at 1 h p.i.). These results warrant further research in larger animals to determine suitability of [123I]‐3‐I‐CO as a 5‐HT2A tracer. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献