4051 research outputs found
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Purification of 2-[18F]fluoro-2-deoxy-d-glucose by on-chip solid-phase extraction
No full textMicrofluidic devices have shown great potential for the production of positron emission tomography (PET) radiotracers, but most devices have focused only on the synthesis step of the procedure, typically neglecting the other important steps such as [18F]fluoride pre-concentration and radiotracer purification that could equally benefit from miniaturisation. Here, we demonstrate the development of microfluidic modules for the purification of PET radiotracers, particularly 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG), via the use of on-chip solid-phase extraction (SPE). In these initial tests, the SPE modules were able to yield [18F]FDG with up to 90% radiochemical purity, and methods are proposed for further increasing this value. © 2013 Elsevier B.V
A new class of fluorinated 5-pyrrolidinylsulfonyl isatin caspase inhibitors for PET imaging of apoptosis
No full textThirteen compounds in a new class of fluorinated 5-pyrrolidinylsulfonyl isatin derivatives were synthesised that have potent and selective inhibitory activity against effector caspases-3 and -7. With in vivo animal PET imaging studies of cerebral ischemia being planned, N-benzylation with selected para-substituted benzylic halides allowed systematic variation of lipophilicity (logP 1.94–3.31) without decreasing inhibition potency (IC50). From this series the p-methoxybenzyl analogue was selected for initial ‘proof-of-concept’ [18F]-fluoride radiolabelling which proceeded in good yield and purity with no need for a protection/deprotection strategy. © 2013 Royal Society of Chemistr
Identification of chemical byproducts in the radiofluorination of structurally complex aryliodonium salts
No full textThe use of direct radiofluorination of aryliodonium salts represents a promising route to new PET tracers. This study tested the use of these precursors for obtaining candidate ligands of the cannabinoid type-2 receptor. 18F-labelling was performed using microfluidic technology, which allowed obtaining good incorporation yields. A closer inspection of the chemical composition of the reaction mixture evidenced the recurrent occurrence of chemical byproducts (H-adduct) due to a reductive side reaction of these substrates. The H-adduct formation seems to be unrelated to water presence, needed for obtaining a satisfactory incorporation, and may become an important feature for assessing the real-life accessibility of new radiotracers through the use of aryliodonium precursors. © 2014 Akadémiai Kiadó, Budapest, Hungar
Effects of precursor solution aging and other parameters on synthesis of ordered mesoporous titania powders
No full textEvaporation-induced self-assembly (EISA) of ordered mesoporous titania powders using block copolymer templates Brij 58 and F127 has been studied as a function of the precursor solution composition and age as well as the evaporation conditions. Small-angle X-ray scattering was used to monitor the degree of order in the mesoporous structure of materials synthesized under these varying conditions. Also, for the first time, the time-dependent formation of Ti structures in precursor solutions and the effect of those structures on the creation of mesostructural order have been demonstrated. The interactions of the Ti precursor with Brij 58 and F127 were investigated and showed that the different templates caused formation of Ti oligomers of unique sizes and structures. Precursor solution composition and evaporation conditions were also shown to affect the order and stability of the mesoporous titania produced. Overall, this systematic study has provided fundamental insights into the synthesis conditions that maximize the degree of order and thermal stability of the final materials. These “optimal” conditions are highly dependent on the choice of template. As a result of this improved understanding, the synthesis of ordered mesoporous titania powders using the block copolymer F127 as a template has been achieved without the use of stabilizing agents for the first time. © 2015 American Chemical Societ
Simulation-based optimisation of the PET data processing for partial saturation approach protocols
No full textPositron emission tomography (PET) with [11C]Raclopride is an important tool for studying dopamine D2 receptor expression in vivo. [11C]Raclopride PET binding experiments conducted using the Partial Saturation Approach (PSA) allow the estimation of receptor density (Bavail) and the in vivo affinity appKD. The PSA is a simple, single injection, single scan experimental protocol that does not require blood sampling, making it ideal for use in longitudinal studies. In this work, we generated a complete Monte Carlo simulated PET study involving two groups of scans, in between which a biological phenomenon was inferred (a 30% decrease of Bavail), and used it in order to design an optimal data processing chain for the parameter estimation from PSA data. The impact of spatial smoothing, noise removal and image resolution recovery technique on the statistical detection was investigated in depth. We found that image resolution recovery using iterative deconvolution of the image with the system point spread function associated with temporal data denoising greatly improves the accuracy and the statistical reliability of detecting the imposed phenomenon. Before optimisation, the inferred Bavail variation between the two groups was underestimated by 42% and detected in 66% of cases, while a false decrease of appKD by 13% was detected in more than 11% of cases. After optimisation, the calculated Bavail variation was underestimated by only 3.7% and detected in 89% of cases, while a false slight increase of appKD by 3.7% was detected in only 2% of cases. We found during this investigation that it was essential to adjust a factor that accounts for difference in magnitude between the non-displaceable ligand concentrations measured in the target and in the reference regions, for different data processing pathways as this ratio was affected by different image resolutions. © 2014 Elsevier B.V.
Evaluating the accuracy of density functional theory for calculating 1H and 13C NMR chemical shifts in drug molecules
No full textThe accuracy of different DFT methodologies for calculating 1H and 13C NMR chemical shifts in (R)-ispinesib, a complex drug molecule with multiple chemical groups and one stereocentre, has been evaluated. The accuracy of 6 basis sets and 16 different XC functionals was tested. In addition, we present a detailed study on the role of geometry optimisation (in gas and solution phase using a chloroform polarisable continuum model) on the accuracy of the calculated NMR spectra. NMR calculations using the double-ζ basis sets DGDZVP and 6-31++G(d,p) were found to be more accurate (and computationally more efficient) than those using larger triple-ζ basis sets. The O3LYP/DGDZVP methodology in solution phase using a geometry optimised at the same level of theory was found to be the most accurate method with mean absolute errors (MAEs) for 1H and 13C chemical shifts of 0.174 ppm and 3.972 ppm, respectively. Irrespective of the choice of XC or basis set used, complete geometry optimisation in either gas or solvent phase was found to be essential for attaining the highest accuracy in both 1H and 13C calculated chemical shifts. Finally, the role of molecular conformation was examined by calculating the Boltzmann-weighted 1H and 13C chemical shifts. Overall, we demonstrate that DFT shows exceptional promise for use in calculating the NMR chemical shifts in complex drug molecules. In the future, DFT calculations of NMR parameters are set to play an increasingly important role in drug discovery and chemical optimisation. © 2014 Elsevier B.V
One‐step radiosynthesis of 4‐nitrophenyl 2‐[18F]fluoropropionate ([18F]NFP); improved preparation of radiolabeled peptides for PET imaging
No full textThe 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. © 2013 John Wiley & Sons, Ltd
Ascertaining the uitability of aryl sulfonyl fluorides for [18F]radiochemistry applications: a systematic investigation using microfluidics
No full textOptimization of [18F]radiolabeling conditions and subsequent stability analysis in mobile phase, PBS buffer, and rat serum of 12 aryl sulfonyl chloride precursors with various substituents (electron-withdrawing groups, electron-donating groups, increased steric bulk, heterocyclic) were performed using an Advion NanoTek Microfluidic Synthesis System. A comparison of radiochemical yields and reaction times for a microfluidics device versus a conventional reaction vessel is reported. [18F]Radiolabeling of sulfonyl chlorides in the presence of competing nucleophiles, H-bond donors, and water was also assessed and demonstrated the versatility and potential utility of [18F]sulfonyl fluorides as synthons for indirect radiolabeling. © 2013 American Chemical Societ
Sodium uptake in cell construction and subsequent in operando electrode behaviour of Prussian blue analogues, Fe[Fe(CN)6]1−x·yH2O and FeCo(CN)6
No full textThe development of electrodes for ambient temperature sodium-ion batteries requires the study of new materials and the understanding of how crystal structure influences properties. In this study, we investigate where sodium locates in two Prussian blue analogues, Fe[Fe(CN)6]1-x·yH2O and FeCo(CN)6. The evolution of the sodium site occupancies, lattice and volume is shown during charge-discharge using in situ synchrotron X-ray powder diffraction data. Sodium insertion is found to occur in these electrodes during cell construction and therefore Fe[Fe(CN)6]1-x·yH2O and FeCo(CN)6 can be used as positive electrodes. NazFeFe(CN)6 electrodes feature higher reversible capacities relative to NazFeCo(CN)6 electrodes which can be associated with a combination of structural factors, for example, a major sodium-containing phase, ∼Na0.5FeFe(CN)6 with sodium locating either at the x = y = z = 0.25 or x = y = 0.25 and z = 0.227(11) sites and an electrochemically inactive sodium-free Fe[Fe(CN)6]1-x·yH2O phase. This study demonstrates that key questions about electrode performance and attributes in sodium-ion batteries can be addressed using time-resolved in situ synchrotron X-ray diffraction studies. © 2014 Royal Societies of Chemistr
Time history of a human kidney stone determined by bomb-pulse dating
No full textAn in vivo grown human kidney stone was dated using the atmospheric bomb pulse. The growth period was found to be 17.6 yr for a sample size of 6 mm across. The step dissolution method was used, as one of several possibilities, to produce depositional subsamples. A noticeable dead carbon presence is detected in the modern industrialized diet, and as a consequence in human metabolites. The importance for correction when applying bomb-pulse dating is noted. © 2016 Arizona Board of Regents on behalf of the University of Arizon