Browsing by Author "Chen, Z"

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    [18F]Ethenesulfonyl fluoride as a practical radiofluoride relay reagent
    (John Wiley & Sons, Inc, 2019-04-11) Zhang, B; Fraser, BH; Klenner, MA; Chen, Z; Liang, SH; Massi, M; Robinson, AJ; Pascali, G
    Fluorine-18 is the most utilized radioisotope in positron emission tomography (PET), but the wide application of fluorine-18 radiopharmaceuticals is hindered by its challenging labelling conditions. As such, many potentially important radiotracers remain underutilized. Herein, we describe the use of [18F]ethenesulfonyl fluoride (ESF) as a novel radiofluoride relay reagent that allows radiofluorination reactions to be performed in minimally equipped satellite nuclear medicine centres. [18F]ESF has a simple and reliable production route and can be stored on inert cartridges. The cartridges can then be shipped remotely and the trapped [18F]ESF can be liberated by simple solvent elution. We have tested 18 radiolabelling precursors, inclusive of model and clinically used structures, and most precursors have demonstrated comparable radiofluorination efficiencies to those obtained using a conventionally dried [18F]fluoride source. © 2019 Wiley-VCH Verlag GmbH & Co.
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    Additively manufactured Haynes-282 monoliths containing thin wall struts of varying thicknesses
    (Elsevier, 2022-09-01) Lim, B; Chen, H; Nomoto, K; Chen, Z; Saville, AI; Vogel, SC; Clarke, AJ; Paradowska, AM; Reid, M; Primig, S; Liao, XZ; Babu, SS; Breen, AJ; Ringer, SP
    Magnitude and distribution of residual stresses in additively manufactured Ni-based superalloys may impact the mechanical performance of as-fabricated parts. Though electron beam powder bed fusion (E-PBF) can produce components with minimal defects and residual stresses compared to laser powder bed fusion and directed energy deposition, variations of them may occur within the complex geometry of a component, due to inherent variations of thermal signatures and the evolution of section modulus along the build direction. This work reveals the residual stress distribution, characterised from neutron diffraction, of an as-fabricated Haynes 282 monolith containing internal cube voids and thin wall struts of varying thicknesses. Complementary local hardness measurements and multi-scale microscopy were used to investigate the geometry-structure-property relationships. Observed variations in hardness were attributed to a combination of type I macro-scale residual stresses and variations in bimodal γ′ precipitation behaviour. The results highlight the influence of residual stresses and microstructure on the mechanical properties of E-PBF Haynes 282. © 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
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    Effects of mutations in the NMDA receptor GluN1 subunit on binding and dynamics: a computational approach
    (International Union of Crystallography, 2021-08-14) Chen, Z; Church, WB; Bastard, K; Duff, AP; Balle, T
    N-methyl-D-aspartate receptors (NMDARs) are central to the pathophysiology of neurodegenerative diseases such as schizophrenia [1], however despite significant structural insights of the receptor [2,3,4,5] the importance of mutations in the NMDAR have been poorly described in the literature. Here we present molecular dynamics simulation data combined with modelling and binding free energy calculations to outline the effects of mutations [6] in the GluN1 subunit of the NMDAR on agonist binding affinity and ligandreceptor interactions. Our data demonstrates the changes caused by the positioning of an introduced tyrosine residue at the binding pocket and its associated changes in the conformation upon ligand binding. Furthermore, molecular dynamics simulations demonstrate the changes in ligand environment in the ligand-receptor complex leading to a loss of key interactions and an associated instability of the bound complex. Lastly, binding free energy calculations show that it is no longer energetically favourable for ionic interactions to form and an associated overall increase in Gibbs free energy for ligand binding. These data are important in explaining the changes in behaviour for mutations in the GluN1 ligand binding region and are consistent with previously reported experiments [7]. We are also pursuing experimental approaches to further understand the action of ligand binding. © 2021 The Authors
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    A novel [18F]fluoride relay reagent for radiofluorination reactions
    (John Wiley & Sons, Inc, 2019-05-26) Zhang, B; Fraser, BH; Klenner, MA; Chen, Z; Liang, SH; Massi, M; Robinson, AJ; Pascali, G
    Objectives Fluorine‐18 is the most utilized radioisotope in Positron Emission Tomography (PET), but the wide application of fluorine‐18 radiopharmaceuticals is hindered by its challenging labelling conditions. This necessitates production at centralized PET centres with highly specialized equipment including cyclotrons, hot cells, synthesizers, and HPLC capabilities, which ultimately limit the availability of fluorine‐18 tracers to those whose production has a large marketing scale (e.g., [18F]FDG). As such, many potentially important leads remain underutilized. Herein, we describe the use of [18F]ethenesulfonyl fluoride (ESF) as a novel radiofluoride relay reagent that allows radiofluorination reactions to be performed in minimally equipped satellite nuclear medicine centres (Figure 1). Methods [18F]ESF was produced from 2,4,6‐trichlorophenylethenesulfonate using a microfluidic system and was stored on inert cartridges. The cartridges could be shipped remotely where trapped [18F]ESF was liberated by chosen solvent to a vial containing precursor and additives. The reaction mixture was then stirred and heated using a heating block. Reaction conditions including temperature, time, precursor concentration, and additives were optimised, and the radiochemical yields (RCYs) were compared with those for traditional [18F]fluoride method. Results We found that conditions of 1 mg/mL precursor, 0.5 mg/mL tetraethylammonium bicarbonate as additive, temperature of 100°C, and time of 15 min were useful to assess radiofluorination scope on commercially available precursors. The obtained RCYs were compared with those generated from traditional dried [18F]fluoride source and no statically significant difference was observed for most precursors. Some differences on RCYs, both positive and negative, were noted when novel type of precursors (i.e., boronic acids, iodonium ylides) were tested. Conclusions We have developed a method to perform radiofluorinations using a new radiofluoride relay reagent, [18F] ESF. Such method reduces the reaction equipment needed, in the simplest case to a simple heating block, single‐use vials and magnetic stir bar. Notably, this new process is not only compatible with typical commercial precursors, but also feasible to accommodate emerging precursors with novel leaving groups. © 2019 The Authors