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1.
[18F]Xenon difluoride ([18F]XeF2), was produced by treating xenon difluoride with cyclotron-produced [18F]fluoride ion to provide a potentially useful agent for labeling novel radiotracers with fluorine-18 (t1/2 = 109.7 min) for imaging applications with positron emission tomography. Firstly, the effects of various reaction parameters, for example, vessel material, solvent, cation and base on this process were studied at room temperature. Glass vials facilitated the reaction more readily than polypropylene vials. The reaction was less efficient in acetonitrile than in dichloromethane. Cs+ or K+ with or without the cryptand, K 2.2.2, was acceptable as counter cation. The production of [18F]XeF2 was retarded by K2CO3, suggesting that generation of hydrogen fluoride in the reaction milieu promoted the incorporation of fluorine-18 into xenon difluoride. Secondly, the effect of temperature was studied using a microfluidic platform in which [18F]XeF2 was produced in acetonitrile at elevated temperature (≥85 °C) over 94 s. These results enabled us to develop a method for obtaining [18F]XeF2 on a production scale (up to 25 mCi) through reaction of [18F]fluoride ion with xenon difluoride in acetonitrile at 90 °C for 10 min. [18F]XeF2 was separated from the reaction mixture by distillation at 110 °C. Furthermore, [18F]XeF2 was shown to be reactive towards substrates, such as 1-((trimethylsilyl)oxy)cyclohexene and fluorene.  相似文献   

2.
Vasoactive intestinal peptide (VIP) receptors are expressed on various tumor cells in much higher density than somatostatin receptors, which provides the basis for radiolabeling VIP as tumor diagnostic agent. However, fast proteolytic degradation of VIP in vivo limits its clinical application. With the aim to develop and evaluate new ligands for depicting the VIP receptors with positron emission tomography (PET), the structure modified [R8,15,21, L17]-VIP analog was radiolabeled with 18F using two different methods. With the first method, N-4-[18F]fluorobenzoyl-[R8,15,21, L17]-VIP ([18F]FB-[R8,15,21, L17]-VIP 7) was produced in a decay-corrected radiochemical yield (RCY) of 33.6 ± 3%, a specific radioactivity of 255 GBq/μmol (n = 5) within 100 min in four steps. Similarly, N-4-[18F](fluoromethyl)-benzoyl-[R8,15,21, L17]-VIP ([18F]FMB-[R8,15,21, L17]-VIP 8) was synthesized in a RCY of 34.85 ± 5%, a specific radioactivity of 180 GBq/μmol (n = 5) within 60 min in only one step. The two products 7 and 8 were both shown good stability in HSA. Moreover, the low bone uptakes of 7 and 8 in vivo of mice showed good defluorination stability.  相似文献   

3.
18F-labeled compounds play a major role in the development of new in vivo imaging agents for Positron Emission Tomography (PET), a non invasive imaging modality depicting the biodistribution of radioactive compounds in humans. Recently we reported a new method for the introduction of fluorine-18 into a range of organic molecules exploiting the very fast 18F-19F isotope exchange of fluorosilanes (termed SiFA compounds). Here, we wish to report the labeling of the first charged SiFA molecule N-(4-(di-tert-butylfluorosilyl)benzyl)-2-hydroxy-N,N-dimethylethylammonium bromide (SiFAN+Br) serving as a lead compound in the development of SiFA-based prosthetic groups of reduced lipophilicity for biomolecule labeling. Mild conditions for synthesis of [18F]SiFAN+Br and an easy purification procedure using simple C-18 solid phase cartridge have been developed yielding the [18F]SiFAN+Br in radiochemical yields of 34% (non-decay corrected) within 40 min. A series of kinetic experiments were performed that show high isotopic exchange rate constants. Low activation energy (15.7 kcal/mol) and a large preexponential factor (7.9 × 1013 M−1 s−1) were calculated for the isotopic exchange reaction from a corresponding Arrhenius plot. For comparison, the 18F-fluorination of ethyleneglycol-di-p-tosylate via the formation of a carbon-18F bond showed a 1.3 kcal/mol higher activation energy and a much lower preexponential factor of 2.9 × 109 M−1 s−1. Moderate hydrophilicity (log D = 0.44), stability in aqueous media at pH up to 7.4 and a high specific activity of [18F]SiFAN+Br (SA = 20.4 GBq/μmol, 0.55 Ci/μmol) make this charged SiFA compound useful for the development of novel SiFA-based 18F-labeling synthons.  相似文献   

4.
2-Fluoro-1,3-thiazoles were rapidly and efficiently labeled with no-carrier-added fluorine-18 (t1/2 = 109.7 min) by treatment of readily prepared 2-halo precursors with cyclotron-produced [18F]fluoride ion. The [18F]2-fluoro-1,3-thiazolyl moiety constitutes a new and easily-labeled structural motif for prospective molecular imaging radiotracers.  相似文献   

5.
Strained tricyclic ring systems such as epoxides are rarely used as precursors for the introduction of anionic fluorine-18 into organic compounds intended for positron emission tomography (PET). Here we report the alpha selective ring opening of epoxides for the introduction of fluorine-18 into small as well as larger biomolecules via 1- and 2-step protocols. [18F]fluoromisonidazole ([18F]MISO), a tracer for hypoxia imaging, and the tumor targeting peptide Tyr3-octreotate (TATE) were radiolabeled using epoxide opening reactions. In the latter case, the new prosthetic labeling synthon 4-(3-[18F]fluoro-2-hydroxypropoxy)benzaldehyde ([18F]FPB) has been used for 18F-introduction.  相似文献   

6.
Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [89Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [18F]-fluorodeoxyglucose ([18F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [89Zr]-pertuzumab mean standard uptake values (SUVmean) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [18F]-FDG SUVmean changes were negatively correlated with [89Zr]-pertuzumab SUVmean (r = −0.5887, p = 0.0030). The baseline [18F]-FDG SUVmean was negatively correlated with initial [89Zr]-pertuzumab SUVmean (r = −0.6852, p = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.  相似文献   

7.
Since many molecules bearing quinoline-5,8-dione or fused 1,4-quinone moieties possess a wide spectrum of biological activities, efficient methods for incorporation of fluorine-18 (F-18) into quinoline-5,8-diones have received considerable attention in positron emission tomography (PET) molecular imaging studies. In this paper, we describe an efficient synthetic route for the regioselective preparation of fluoropropyl-substituted quinoline-5,8-diones on the C3, C4, and C6 positions by tert-alcohol media fluorination, followed by oxidative demethylation of the corresponding dimethoxy compound using N-bromosuccinimide (NBS) in the presence of catalytic amounts of sulfuric acid. Moreover, F-18 labeled [18F]fluoropropylquinoline-5,8-diones [18F]21-23 were prepared from the corresponding mesylate precursors by a method of rapid and efficient one-pot, two-step reactions: radiofluorination using TBA [18F]F generated under no-carrier-added (NCA) conditions; oxidative demethylation, resulting in a 45% radiochemical yield of [18F]21-23 (decay-corrected) with a total synthesis time (including HPLC purification) of 75 min and high radiochemical purity (>99%), as well as high specific activity (∼230 GBq/μmol).  相似文献   

8.
As model reactions for the introduction of [18F]fluorine into aromatic amino acids, the replacement of NO2 by [18F]fluoride ion in mono- to tetra-methoxy-substituted ortho-nitrobenzaldehydes was systematically investigated. Unexpectedly, the highly methoxylated precursors 2,3,4-trimethoxy-6-nitrobenzaldehyde and 2,3,4,5-tetramethoxy-6-nitrobenzaldehyde showed high maximum radiochemical yields (82% and 48% respectively). When the electrophilicity of the leaving group substituted carbon atom is expressed by its 13C NMR chemical shift a good correlation with the reaction rate at the beginning of the reaction (first min) was found (R2 = 0.89), whereas the maximum radiochemical yields correlated much poorer with this electrophilicity parameter. This may be caused by side reactions becoming influencial in the further reaction course. As possible side reactions the demethylation of methoxy groups and intramolecular redox reactions could be detected by HPLC/MS.  相似文献   

9.
Positron emission tomography (PET) imaging of activated T-cells with N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding due to complex and time-consuming chemical processes. Herein, we report an improved method for the synthesis of [18F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [18F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [18F]fluoride, 3.8 times higher than previously reported methods. In vitro experiments showed that the radiotracer was stable with good radiochemical purity (>95%), confirmed its identity and showed preferential binding to activated mouse peripheral blood mononuclear cells. Dynamic PET imaging and ex vivo biodistribution studies in naïve Balb/c mice showed organ distribution and kinetics comparable to earlier published data on [18F]FB-IL-2. Significant improvements in the radiochemical manufacture of [18F]FB-IL-2 facilitates access to this promising PET imaging radiopharmaceutical, which may, in turn, provide useful insights into different tumour phenotypes and a greater understanding of the cellular nature and differential immune microenvironments that are critical to understand and develop new treatments for cancers.  相似文献   

10.
Polyelectrolytes were incorporated into porous reinforcing materials to study the properties of ionomers in confined spaces and to determine the effect of the porous material on the behaviour of the membranes. Nafion® was imbibed into porous polypropylene (Celgard®), ultra-high-molecular weight polyethylene (Daramic®), and polytetrafluoroethylene (PTFE) films. Through the use of reinforcing materials, it is possible to prepare membranes that are thinner, but stronger than pure ionomer membranes. Thin reinforced membranes have advantages such as lower areal resistance (as low as 0.14 Ω cm2 for 57 μm CG3501 + Nafion® compared to 0.34 Ω cm2 for 89 μm cast Nafion®) and lower dimensional changes due to swelling (as low as a 4% change in length and width for WDM + Nafion® compared to 13% for cast Nafion®). Using reinforcing materials results in a reduction in important membrane properties compared to bulk Nafion®, such as proton conductivity (as low as 0.016 S cm−1 for CG3401 + Nafion® compared to 0.076 S cm−1 for cast Nafion®), effective proton mobility (as low as 3.2 × 10−4 cm2 V−1 s−1 CG3401 + Nafion® compared to 7.6 × 10−4 cm2 V−1 s−1 for cast Nafion®), and water vapour permeance (as low as 0.036 g h−1 Pa−1 m−2 for WDM + Nafion® compared to 0.056 g h−1 Pa−1 m−2 for cast Nafion®). By normalizing the membrane properties with respect to ionomer content, it was possible to examine the properties of the Nafion® inside the pores of the membranes. The proton conductivity (as low as 0.032 S cm−1 for CG3401 + Nafion®), effective proton mobility (as low as 3.6 × 10−4 cm2 V−1 s−1 for CG3401 + Nafion®), and water vapour permeability (as low as 2.7 × 10−6 g h−1 Pa−1 m−1 for PTFE MP 0.1 + Nafion®) of the ionomer in the membrane are also diminished compared to bulk Nafion® due to decreased connectivity of the ionomer and a restriction in macromolecular motions caused by the pore walls. A series of porous materials with increasing pore were also examined. As the pore size of the PTFE MP materials increased from 0.1 μm to 10 μm, the proton conductivity (0.022 S cm−1 to 0.041 S cm−1), effective proton mobility ((4.1 to 5.6) × 10−4 cm2 V−1 s−1), and water vapour permeability ((2.4 to 4.3) × 10−6 g h−1 Pa−1 m−1) of the reinforced membranes improved with increasing pore size and the properties of the ionomer inside the membranes approached the value of bulk Nafion®.  相似文献   

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