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1.
Neolignans honokiol and 4′-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [11C]MPbP (4′-[11C]methoxy-5-propyl-1,1′-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4′-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1′-biphenyl (F-IV) was selected for labeling with fluorine-18 (T1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [18F]F-IV in a rodent model of neuroinflammation. [18F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by 18F-fluoroethylation of the precursor with Boc-protecting group (15) with [18F]2-fluoro-1-bromoethane ([18F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [18F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [11C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [18F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.  相似文献   

2.
A series of activated carbons with high mesoporous ratio were prepared by KOH reactivation based on activated carbon as the precursor. As the KOH/AC mass ratio was increased to 4:1, the mesoporous ratio increases from 60% to 76%, and the average pore size from 2.23 to 3.14?nm. Moreover, the specific capacitance for the activated carbon in ionic liquid 1-ethyl-3-methylmidazolium tetrafluoroborate ([EMIm]BF4) can reach the maximum value of 189?F?g?1 (8.0???F?cm?2). In addition, the decrease of specific capacitance for activated carbons by KOH reactivation with current density increase shows two regimes, suggesting that activated carbons with high mesoporous ratio are much fit for charge?Cdischarge at larger current density.  相似文献   

3.
A potential dopamine D4 receptor ligand, 1-(4-(4-(4-fluorobenzyl)-1-piperazinyl)butyl)indolin-2-one (4) was synthesized through a four-step process and its affinity and selectivity for dopamine D2-like receptors was determined through in vitro receptor binding assay. [18F]4 was prepared using a one-pot two-step method with total radiochemical yield 21.2 % (decay-corrected). The molar radioactivity was around 135 GBq/μmol and the radiochemical purity was greater than 95.5 %. The partition coefficient (Log P) of [18F]4 was determined to be 2.10 ± 0.30 through octanol experiment. The in vivo biodistribution and the competitive distribution of [18F]4 in rat exposed that the tracer passes through blood–brain-barrier (BBB) and may specifically bind to D4 receptor. Metabolite analysis revealed that there was no metabolism of [18F]4 in brain. Conclusively, these preliminary results demonstrated that [18F]4 shows promises as a radioligand for the in vivo study of dopamine D4 receptor.  相似文献   

4.
3-(4-[18F]fluorobenzyl)-8-hydroxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one ([18F]FHTP) was in vitro and in vivo evaluated as a putative dopamine D4 receptor radioligand. Its inhibition constant (K i ) for cloned human dopamine D4.2 receptor was determined to be 2.9 nM and it displayed a 2000-fold D4-selectivity over the D2long subtype. Its partition coefficient (logP) was measured to be 1.11. Biodistribution, blocking distribution and metabolism studies in rats demonstrated that the specific distribution of [18F]FHTP in brain regions, suggesting that [18F]FHTP may be a suitable PET imaging agent for in vivo studies of the dopamine D4 receptor.  相似文献   

5.
A Co(OH)2/graphene sheet-on-sheet hybrid has been fabricated by in situ one-step hydrothermal growth for electrochemical pseudocapacitors application. The hybrid delivers a specific capacitance of 436 F?g?1 at a current density of 50 A?g?1. Besides, it can keep a specific capacitance of 651 F?g?1 after 10,000 cycles at 10 A?g?1. The excellent performance can be ascribed to the high-quality graphene matrix, regular morphology and high crystallinity of Co(OH)2, and unique sheet-on-sheet structure of the hybrid, endowing enhanced transportation of electrons and Faradic redox reactions. The results demonstrate that the Co(OH)2/graphene hybrid with a sheet-on-sheet structure is promising for high-performance energy storage applications.  相似文献   

6.
This study describes a convenient protocol for the synthesis of (2S)-tert-butyl 2-(2-bromopropanamido)-5-oxo-5-(tritylamino)pentanoate, which can serve as an appropriate precursor of (2S)-5-amino-2-(2-[18F]fluoropropanamido)-5-oxopentanoic acid (N-(2-[18F]fluoropropionyl)-L-glutamine, [18F]FPGLN) for tumor positron emission tomography imaging. Five-step synthesis starting from L-glutamine provided the desired precursor with high yields. In addition, a simple method for the preparation of [18F]FPGLN from this easily available precursor was developed using a two-step 18F-labeling strategy.  相似文献   

7.
Radiochemical 18F-fluorination yields of several compounds using the secondary labelling precursors 2-[18F]fluoroethyl tosylate ([18F]FETos) and 1-bromo-2-[18F]fluoroethane ([18F]BFE) could be considerably enhanced by the addition of an alkali iodide. The radiochemical yield of [18F]fluoroethyl choline for example could be doubled with [18F]BFE and increased from 13% to ≈80% with [18F]FETos. By addition of alkali iodide to the precursor, the 18F-fluoroethylation yields of established radiopharmaceuticals, especially in the case of automated syntheses, could be significantly increased without major changes of the reaction conditions.  相似文献   

8.
Nucleophilic incorporation of [18F]F? under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to 18F‐labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4‐formyl‐, 3‐formyl‐, 4‐maleimido‐ and 4‐oxylalkynl‐arylsulfonyl [18F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[18F]F/Cs2CO3(aq.) in a reaction time of 15 min at room temperature. With the exception of 4‐N‐maleimide‐benzenesulfonyl fluoride ( 3 ), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [18F]fluorination (1:1:0.8 tBuOH/Cs2CO3(aq.)/pyridine) did not negatively affect yields of 3‐formyl‐2,4,6‐trimethylbenzenesulfonyl [18F]fluoride ( 2 ) and dramatically improved the yields of 4‐(prop‐2‐ynyloxy)benzenesulfonyl [18F]fluoride ( 4 ). The N‐arylsulfonyl‐4‐dimethylaminopyridinium derivative of 4 ( 14 ) can be prepared and incorporates 18F efficiently in solutions of 100 % aqueous Cs2CO3 (10 mg mL?1). As proof‐of‐principle, [18F] 2 was synthesised in a preparative fashion [88(±8) % decay corrected (n=6) from start‐of‐synthesis] and used to radioactively label an oxyamino‐modified bombesin(6–14) analogue [35(±6) % decay corrected (n=4) from start‐of‐synthesis]. Total preparation time was 105–109 min from start‐of‐synthesis. Although the 18F‐peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature 18F labelling strategy.  相似文献   

9.
A new automated synthesis procedure of 1-H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([18F]FMISO), a specific hypoxia imaging agent with great significances for the noninvasive, dynamic hypoxia evaluation of cancer, was developed by modifying Explora FDG4 module, a commercial [18F]FDG production system, in this study. Its radiochemical synthesis was carried out via two sequent reaction steps, i.e. the nucleophilic displacement of labeling precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) with activated 18F- ion at 100 °C for 8 minutes, and the following hydrolysis with 1M HCl at 100 °C for 5 minutes and neutralization with 1M NaOH. Two-pot reaction with two independent separations was adopted to assure the good separation of final product via solid phase extraction (SPE) based upon combined Sep-pak cartridges instead of high performance liquid chromatography (HPLC). This fast, reliable preparation route of 18F-FMISO could complete within 50 minutes with about 55% of high radiochemical yield (with decay correction) and more than 98% of good radiochemical purity. The modified module could perform multiple runs of production of [18F]FMISO.  相似文献   

10.
Hierarchical mesoporous carbon materials with large microporosity were prepared by direct tri-constituent co-assembly with the use of resols as the carbon precursor, tetraethyl orthosilicate as the inorganic precursor, and triblock copolymer F127 as the soft template. Bimodal pore size distributions in the range of 1.5–4 and 7.5–12 nm were obtained in the synthesized hierarchical mesoporous carbon materials after etching of silica by HF acid, showing a high surface area of 1,675 m2?g?1 with a large pore volume of 2.06 cm3?g?1. The electrochemical performance of the hierarchical mesoporous carbons was evaluated as an electrode material for electrochemical supercapacitor, showing a specific capacitance as high as 152 F?g?1 at a scan rate of 5 mV?s?1 in 6 M KOH aqueous solution and a good cycling stability with capacitance retention of 99 % over 500 cycles.  相似文献   

11.
In cancer cells hypoxia can cause resistance to both radio- and chemo-therapy. Being able to quantify, the degree of hypoxia in the cells is a useful tool in therapy planning. The positron emitting 1-[18F]fluoro-3-(2-nitro-1H-imidazol-1-yl)propan-2-ol ([18F]FMISO) is the most extensively used tracer for imaging hypoxia. Automated synthesis of [18F]FMISO was set up on IBA Synthera®. The precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-p-toluenesulfonyl propanediol (NITTP) was heated at 100 °C for 10 min with [K/K 2.2.2.]+[18F]? and thereafter hydrolyzed with 0.1 M hydrochloric acid at 90 °C for 2 min. Purification was performed on solid-phase extraction (SPE) cartridges. [18F]FMISO was obtained in 50 ± 3 % (n = 6) radiochemical yield (decay-corrected) in 35 min synthesis time with radiochemical purity of ≥98 %. The use of disposable Integrated Fluid Processors (IFP?:s) and cartridge purification simplifies the handling and shortens the synthesis time. This is a no frills setup based on all commercially available materials and the synthesis is performed with minor changes from the FDG time-list.  相似文献   

12.
A new and simple high-performance liquid chromatography with evaporative light scattering detector method for the determination of Kryptofix 2.2.2 (K-222) in the radiopharmaceuticals of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) was developed. A C18 column was used and the mobile phase was 10?% (v/v) methanol and 90?% (v/v) water (0.1?% trifluoroacetic acid, v/v) at a flow rate of 0.2?mL?min?1. The drift tube temperature was 40?°C. The pressure of nebulizing gas (N2) was 3.0?bar. The gain was 10. Good separation of K-222 from main related substances could be achieved. Excellent linearity (r 2?=?0.9995) was obtained over the range of 5–100?μg?mL?1. The precision ranged from 0.68 to 5.16?% (RSD) and the accuracy ranged from ?3.05 to 2.62?% (RE). The limit of detection was 2?μg?mL?1. This method offers simple, rapid and quantitative detection of K-222, thus making it acceptable for routine determination.  相似文献   

13.
The serotonin receptor 5-HT1A ligand 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was produced by a simplified method of Le Bars et al. Traditional oil bath heating was compared to microwave heating. Various radioanalytical methods, radio-Thin Layer Chromatography (TLC), High Pressure Liquid Chromatography (HPLC) and Mass Spectrometry (MS), were compared in the evaluation of the labelled product(s). The crude reaction mixture consisted of p-[18F]MPPF and 2–4 radioactive by-products eluting after the product fraction, and the reverse-phase HPLC method failed occasionally to separate p-[18F]MPPF from the radioactive by-product with close retention time. The heating method had no significant effect on the composition of labelled by-products. In LC-(ESI)-MS analysis of p-[18F]MPPF the labelled product was identified with m/z ratio of 435 ([M + H+]). The other HPLC fractions were measured to have following m/z ratios: (1) 327; 349; (675) (2) 402; 407/408; (791) and (3) 436, suggesting different kind of decomposition of the labelled product and/or the inactive precursor. The ion trap mass spectrometer was sufficient for the qualitative analysis of p-[18F]MPPF. However, differentiation of by-products arising from the decomposition of p-[18F]MPPF or from its precursor p-MPPNO2 proved to be challenging.  相似文献   

14.
(1) Background: [18F]Flumazenil 1 ([18F]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABAA in the brain. The production of [18F]FMZ 1 for its clinical use has proven to be challenging, requiring harsh radiochemical conditions, while affording low radiochemical yields. Fully characterized, new methods for the improved production of [18F]FMZ 1 are needed. (2) Methods: We investigate the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of [18F]FMZ 1 that is suitable for clinical use. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. (3) Results: The radiosynthesis of [18F]FMZ 1 was fully automated using the iPhase FlexLab radiochemistry module, affording a 22.2 ± 2.7% (n = 5) decay-corrected yield after 80 min. [18F]FMZ 1 was obtained with a high radiochemical purity (>98%) and molar activity (247.9 ± 25.9 GBq/µmol). (4) Conclusions: The copper-mediated radiofluorination of the stannyl precursor is an effective strategy for the production of clinically suitable [18F]FMZ 1.  相似文献   

15.
Central nervous system tumors related to gliomas are of neuroectodermal origin and cover about 30% of all primary brain tumors. Glioma is not susceptible to any therapy and surgical attack remains one of the main approaches to its treatment. Preoperative tumor imaging methods, such as positron emission tomography (PET), are currently used to distinguish malignant tissue to increase the accuracy of glioma removal. However, PET is lacking a specific visualization of cells possessing certain molecular markers. Here, we report an application of aptamers to enhancing specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Glioblastoma is characterized by increased EGFR expression, as well as mutations of this receptor associated with active division, migration, and adhesion of tumor cells. Since 2021, EGFR has been included into the WHO classification of gliomas as a molecular genetic marker. To obtain conjugates of aptamers GR20 and GOL1-specific to EGFR, a 4-[18F]fluorobenzylazide radiotracer was used as a synthon. For the production of the synthon, a method of automatic synthesis on an Eckert & Ziegler research module was adapted and modified using spirocyclic iodonium ylide as a precursor. Conjugation of 4-[18F]fluorobenzylazide and alkyne-modified aptamers was carried out using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with/without the TBTA ligand. As a result, it was possible to obtain 18F-labelled conjugates with 97% radiochemical purity for [18F]FB-GR20 and 98% for [18F]FB-GOL1. The obtained conjugates can be used for further studies in PET analysis on model animals with grafted glioblastoma.  相似文献   

16.
3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a positron emission tomography (PET) tracer useful for tumor proliferation assessment for a number of cancers, particularly in the cases of brain, lung, and breast tumors. At present [18F], FLT is commonly prepared by means of the nucleophilic radiofluorination of 3-N-Boc-5′-O-DMT-3′-O-nosyl thymidine precursor in the presence of a phase-transfer catalyst, followed by an acidic hydrolysis. To achieve high radiochemical yield, relatively large amounts of precursor (20–40 mg) are commonly used, leading to difficulties during purification steps, especially if a solid-phase extraction (SPE) approach is attempted. The present study describes an efficient method for [18F]FLT synthesis, employing tetrabutyl ammonium tosylate as a non-basic phase-transfer catalyst, with a greatly reduced amount of precursor employed. With a reduction of the precursor amount contributing to lower amounts of synthesis by-products in the reaction mixture, an SPE purification procedure using only two commercially available cartridges—OASIS HLB 6cc and Sep-Pak Alumina N Plus Light—has been developed for use on the GE TRACERlab FX N Pro synthesis module. [18F]FLT was obtained in radiochemical yield of 16 ± 2% (decay-corrected) and radiochemical purity >99% with synthesis time not exceeding 55 min. The product was formulated in 16 mL of normal saline with 5% ethanol (v/v). The amounts of chemical impurities and residual solvents were within the limits established by European Pharmacopoeia. The procedure described compares favorably with previously reported methods due to simplified automation, cheaper and more accessible consumables, and a significant reduction in the consumption of an expensive precursor.  相似文献   

17.
Nickel oxide/expanded graphite (NiO/EG) nanocomposites with different loading of EG were prepared through chemically depositing Ni(OH)2 in EG followed by thermal annealing and characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Brunauer–Emmet–Teller (BET) isotherm and electrochemical measurements. The prepared NiO/EG composites were found to be crystalline and highly porous with high specific surface area and pore volume. SEM analysis reveals uniform porous morphology for NiO in the NiO/EG-60 nanocomposites which shows good specific capacitance (510?F?g?1) at a current density of 100?mA?g?1 in 6?mol?L?1 KOH measured by chronopotentiometry employing a three-electrode system. The specific capacitance retention of the NiO/EG-60 nanocomposites was found to be ca. 95% after 500 continuous galvanostatic charge–discharge cycles, indicating that the NiO/EG nanocomposites can become promising electro-active materials for supercapacitor application.  相似文献   

18.
Owing to their broad spectrum of biological activities and low toxicity, β‐lactams are attractive lead structures for the design of novel molecular probes. However, the synthesis of positron emission tomography (PET)‐isotope‐labelled β‐lactams has not yet been reported. Herein, we describe the simple preparation of radiofluorinated β‐lactams by using the fast Kinugasa reaction between 18F‐labelled nitrone [18F]‐ 1 and alkynes of different reactivity. Additionally, 18F‐labelled fused β‐lactams were obtained through the reaction of a cyclic nitrone 7 with radiofluorinated alkynes [18F]‐ 6 a , b . Radiochemical yields of the Kinugasa reaction products could be significantly increased by the use of different CuI ligands, which additionally allowed a reduction in the amount of precursor and/or reaction time. Model radiofluorinated β‐lactam‐peptide and protein conjugates ([18F]‐ 10 and 18F‐labelled BSA conjugate) were efficiently obtained in high yield under mild conditions (aq. MeCN, ambient temperature) within a short reaction time, demonstrating the suitability of the developed method for radiolabelling of sensitive molecules such as biopolymers.  相似文献   

19.
In homoaromatic systems, isotopic exchange (18F/19F) was previously (J Label Compd Radiopharm 18(12):1721–1730 [2], J Chem Soc Perkin Trans 1(3):295–298 [3]) proven to be advantageous, yet in general specific activity is thought to be low. For heteroaromatic systems, in particular, very few examples are published regarding the 18F-labelling of 2-substituted pyridines (J Label Compd Radiopharm 42:975–985 [9]). Therefore, in 2-fluoropyridines, we decided to study the 18F labelling by isotopic exchange (18F/19F). The radiochemical yield for 2-fluoropyridine was 90 ± 2%. Even if 2-fluoropyridine was substituted by an electron-donating group such as a methyl or a methoxy group, radiochemical yields were 80 ± 1 and 78 ± 1%, respectively. Although in benzenes, these substituents are known to decrease nucleophilic substitutions by 18F-Fluoride significantly. Moreover, by choosing appropriate concentrations of 2-fluoropyridines, reasonably high specific activities up to 10 GBq/μmol were obtained.  相似文献   

20.
Mesoporous carbon nanosheets (MCNs) were synthesized using porous magnesium oxide (MgO) layer as the template precursor and resol as the carbon source. The morphology of the mesoporous carbon particles can be easily controlled by altering the mass ratio of MgO to resol. The structural characterization demonstrates that the interlaced MCNs can be formed when MgO/resol is 1:1 and they possess the carbon nanolayer with a thickness of about 5 nm and a width of about 200 nm. The quantities of mesopores and micropores endow the MCNs with a large surface area of 1,180 m2?g?1 and a high pore volume of 1.56 cm3?g?1. The supercapacitive performance of carbon products synthesized with various MgO/resol ratios was evaluated using cyclic voltammetry and galvanostatic charge–discharge techniques. The results show that the interlaced MCNs exhibit the highest specific capacitance of 241 F?g?1, the best rate capability and cycling stability, which are attributed to the fast electrolyte ion transport or diffusion throughout the electrode matrix and effective utilization of the electrical double-layer capacitance of carbon layer.  相似文献   

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