Browsing by Author "Robinson, AJ"

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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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    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
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    Sulfur - fluorine bond in PET radiochemistry
    (BioMed Central Ltd, 2017-07-17) Pascali, G; Matesic, L; Zhang, B; King, AT; Robinson, AJ; Ung, AT; Fraser, BH
    The importance of the sulfur-fluorine bond is starting to increase in modern medicinal chemistry literature. This is due to a better understanding of the stability and reactivity of this moiety depending on the various oxidation states of sulfur. Furthermore, several commercial reagents used for mild and selective fluorination of organic molecules are based on the known reactivity of S-F groups. In this review, we will show how these examples are translating into the 18F field, both for use as stable tags in finished radiopharmaceuticals and as mildly reactive fluoride-relay intermediates. Finally, we also discuss current opportunities where examples of non-radioactive S-F applications/chemistry may be translated into future 18F radiochemistry applications. © The Authors - Creative Commons Attribution 4.0
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    Synthesis, bioconjugation and stability studies of [18F]ethenesulfonyl fluoride
    (John Wiley & Sons, Inc, 2018-06-20) Zhang, B; Pascali, G; Wyatt, NA; Matesic, L; Klenner, MA; Sia, TR; Guastella, AJ; Massi, M; Robinson, AJ; Fraser, BH
    Fluorine-18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [18F]ethenesulfonyl fluoride ([18F]ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [18F]ESF was optimised using a microfluidic reactor under both carrier-added (c.a.) and no-carrier-added (n.c.a.) conditions, affording, in a straightforward procedure, 30-50% radiochemical yield (RCY) for c.a. [18F]ESF and 60-70% RCY for n.c.a. [18F]ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [18F]ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging. © 2018 John Wiley & Sons, Inc.