Browsing by Author "Liang, SH"

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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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    Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque
    (Wiley, 2013-12-11) Holland, JP; Liang, SH; Rotstein, BH; Collier, TL; Stephenson, NA; Greguric, I; Vasdev, N
    Alzheimer's disease (AD) and related dementias show increasing clinical prevalence, yet our understanding of the etiology and pathobiology of disease-related neurodegeneration remains limited. In this regard, noninvasive imaging with radiotracers for positron emission tomography (PET) presents a unique tool for quantifying spatial and temporal changes in characteristic biological markers of brain disease and for assessing potential drug efficacy. PET radiotracers targeting different protein markers are being developed to address questions pertaining to the molecular and/or genetic heterogeneity of AD and related dementias. For example, radiotracers including [11C]-PiB and [18F]-AV-45 (Florbetapir) are being used to measure the density of Aβ-plaques in AD patients and to interrogate the biological mechanisms of disease initiation and progression. Our focus is on the development of novel PET imaging agents, targeting proteins beyond Aβ-plaques, which can be used to investigate the broader mechanism of AD pathogenesis. Here, we present the chemical basis of various radiotracers which show promise in preclinical or clinical studies for use in evaluating the phenotypic or biochemical characteristics of AD. Radiotracers for PET imaging neuroinflammation, metal ion association with Aβ-plaques, tau protein, cholinergic and cannabinoid receptors, and enzymes including glycogen-synthase kinase-3β and monoamine oxidase B amongst others, and their connection to AD are highlighted. Copyright © 2013 John Wiley & Sons, Ltd.
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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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    Novel fluorinated 8-hydroxyquinoline based metal Ionophores for exploring the metal hypothesis of alzheimer’s disease
    (American Chemical Society, 2015-08-10) Liang, SH; Southon, AG; Fraser, BH; Krause-Heuer, AM; Zhang, B; Shoup, TM; Lewis, R; Volitakis, I; Han, Y; Greguric, I; Bush, AI; Vasdev, Y
    Zinc, copper, and iron ions are involved in amyloid-beta (Aβ) deposition and stabilization in Alzheimer’s disease (AD). Consequently, metal binding agents that prevent metal-Aβ interaction and lead to the dissolution of Aβ deposits have become well sought therapeutic and diagnostic targets. However, direct intervention between diseases and metal abnormalities has been challenging and is partially attributed to the lack of a suitable agent to determine and modify metal concentration and distribution in vivo. In the search of metal ionophores, we have identified several promising chemical entities by strategic fluorination of 8-hydroxyquinoline drugs, clioquinol, and PBT2. Compounds 15–17 and 28–30 showed exceptional metal ionophore ability (6–40-fold increase of copper uptake and >2-fold increase of zinc uptake) and inhibition of zinc induced Aβ oligomerization (EC50s < ∼5 μM). These compounds are suitable for further development as drug candidates and/or positron emission tomography (PET) biomarkers if radiolabeled with 18F. © 2015 American Chemical Society