Browsing by Author "Jackson, TW"

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    Assessment of neuroinflammation in transferred EAE via a translocator protein ligand
    (IntechOpen, 2012-02-03) Mattner, F; Staykova, M; Callaghan, PD; Berghofer, PJ; Ballantyne, P; Grégoire, MC; Fordham, S; Pham, TQ; Rahardjo, GL; Jackson, TW; Linares, D; Katsifis, A
    Neuroinflammation is involved in the pathogenesis and progression of neurological disorders such as Alzheimer's disease and multiple sclerosis (MS) (Doorduin et al., 2008). MS has been considered a T cell-mediated autoimmune disorder of the central nervous system (CNS), characterized by inflammatory cell infiltration and myelin destruction (Hauser et al., 1986) and focal demyelinated lesions in the white matter are the traditional hallmarks of MS. However more recent evidence suggests more widespread damage to the brain and spinal cord, to areas of white matter distant from the inflammatory lesions and demyelination of deep and cortical grey matter (McFarland & Martin, 2007). Experimental autoimmune encephalomyelitis (EAE) is an extensively used model of T-cell mediated CNS inflammation; modelling disease processes involved in MS. EAE can be induced in several species by immunization with myelin antigens or via adoptive transfer of myelin-reactive T cells. The models of EAE in rodents [actively induced and transferred] provide information about different phases [inflammation, demyelination and remyelination] and types [monophasic, chronic-relapsing and chronic-progressive] of the human disease multiple sclerosis and a vast amount of clinical and histopathologic data has been accumulated through the decades. A key aim of current investigations is developing the ability to recognise the early symptoms of the disease and to follow its course and response to treatment. Molecular imaging is a rapidly evolving field of research that involves the evaluation of biochemical and physiological processes utilising specific, radioactive, fluorescent and magnetic resonance imaging probes. However, it is positron emission tomography (PET) and single photon emission computer tomography (SPECT) which, due to their exquisite sensitivity involving specifically designed radiolabelled molecules, that is leading the way in molecular imaging and has greatly enabled the non-invasive “visualisation” of many diseases in both animal models and humans. Furthermore, PET and SPECT molecular imaging are providing invaluable imaging data based on a biochemical-molecular biology interaction rather than from the traditional anatomical view. Increasingly, PET and SPECT radiotracers have been exploited to study or identify molecular biomarkers of disease, monitor disease progression, determining the effects of a drug on a particular pathology and assess the pharmacokinetic behaviour of pharmaceuticals in vivo. Significantly, these new imaging systems provide investigators with an unprecedented ability to examine and measure in vivo biological and pharmacological processes over time in the same animals thus reducing experimental variability, time and costs. Molecular imaging based on the radiotracer principle allows chemical processes ranging from cellular events, to cellular communication and interaction in their environment, to the organisation and function of complete tissue and organs to be studied in real time without perturbation. One of the key benefits of molecular imaging is a technique that allows longitudinal studies vital for monitoring intra-individual progression in disease, or regression with supplementary pharmacotherapies. This is key in animal models of diseases such as MS, where there is significant intra-individual variability in the disease course and severity. Recent investigations have proposed the translocator protein (TSPO; 18 kDa), also known as the peripheral benzodiazepine receptor (PBR), as a molecular target for imaging neuroinflammation (Chen & Guilarte, 2008; Doorduin et al., 2008; Papadopoulos et al., 2006). TSPO (18 kDa) is a multimeric protein consisting of five transmembrane helices, which, in association with a 32 kDa subunit that functions as a voltage dependent anion channel and a 30 kDa subunit that functions as an adenine nucleotide carrier forms part of a hetero-oligomeric complex (McEnery et al., 1992) responsible for cholesterol, heme and calcium transport in specific tissue. TSPO is primarily located on the outer mitochondrial membrane and is predominantly expressed in visceral organs (kidney, heart) and the steroid hormone producing cells of the adrenal cortex, testis and ovaries. In the central nervous system (CNS), TSPO is sparsely expressed under normal physiological conditions, however its expression is significantly upregulated following CNS injury (Chen et al., 2004; Papadopoulos et al., 1997; Venneti et al., 2006; Venneti, et al., 2008). Several studies have identified activated glial cells as the cells responsible for TSPO upregulation in inflamed brain tissue, both in humans and in experimental models (Mattner et al., 2011; Myers et al., 1991a; Stephenson et al., 1995; Vowinckel et al., 1997) and the TSPO ligand [11C]-PK11195 was one of the first PET ligands used for imaging activated microglia in various neurodegenerative diseases (Venneti et al., 2006). Although [11C]-(R)-PK11195 is widely used for imaging of microglia, its considerable high plasma protein binding, high levels of nonspecific binding, relatively poor blood–brain barrier permeability and short half-life, limits its use in brain imaging (Chauveau et al., 2008). Recently, alternative PET radioligands for TSPO including the phenoxyarylacetamide derivative [11C]-DAA1106 and its analogues (Gulyas et al., 2009; Takano et al., 2010; Venneti et al., 2008), the imidazopyridines (PBR111) and its analogues (Boutin et al., 2007a; Fookes et al., 2008) and the pyrazolo[1,5-a]pyrimidine derivatives [18F]-DPA-714 and [11C]-DPA-713 (Boutin et al., 2007b; James et al., 2008) have been investigated. In addition to imaging with PET, recent advances in new generation of hybrid SPECT imaging systems enabling increased resolution and morphological documentation with associated computed tomography have been made for use clinically and preclinically. These advances have created a need and an opportunity for SPECT tracers; particularly those incorporating the longer lived radiotracer iodine-123 (t ½ = 13.2 h), to facilitate extended longitudinal imaging studies. In this study the recently developed high-affinity TSPO, SPECT ligand, 6-chloro-2-(4′-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide or CLINDE , was used to explore the expression of activated glia in a model of transferred EAE (tEAE). [123I]-CLINDE has demonstrated its potency and specificity for TSPO binding, its ability to penetrate the blood-brain barrier and suitable pharmacokinetics for SPECT imaging studies (Mattner et al., 2008). It has also been shown that [123I]-CLINDE was able to detect in vivo inflammatory processes characterized by increased density of TSPO in several animal models (Arlicot et al., 2008; Arlicot et al., 2010; Mattner et al., 2005; Mattner et al., 2011; Song et al., 2010), thus representing a promising SPECT radiotracer for imaging neuroinflammation. The present study aimed to investigate the effectiveness of [123I]-CLINDE to detect and quantify the activated glia and consequently correlate the intensity of TSPO upregulation with the severity of disease in a model of tEAE. © 2022 IntechOpen (Open Access).
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    Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the TracerLab FXFN and TracerLab MXFDG module for imaging the peripheral benzodiazepine receptor with PET
    (Pergamon-Elsevier Science Ltd, 2012-01-01) Bourdier, T; Pham, TQ; Henderson, D; Jackson, TW; Lam, P; Izard, M; Katsifis, A
    [F-18]PBR111 and [F-18]PBR102 are selective radioligands for imaging of the Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated method for the radiosynthesis of [F-18]PBR111 and [F-18]PBR102 in the Tracerlab FXFN (30 +/- 2% radiochemical yield non-decay-corrected for both tracers) and Tracerlab MXFDG (25 +/- 2% radiochemical yield non-decay-corrected for both tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers, radiochemical purity was > 99% and specific activity was > 150 GBq/mu mol after less than 60 min of preparation time. © 2012, Elsevier Ltd.
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    Capability development for the quantification of Ba-133 in milk powder by gamma-ray spectrometry
    (South Pacific Environmental Radioactivity Association, 2018-11-06) Van De Voorde, R; Mokhber-Shahin, L; Harrison, JJ; van Wyngaardt, WM; Jackson, TW
    Barium-133 (Ba-133) is a fission product with a half-life of 10.5 years. It decays to its daughter radionuclide Cs-183 by electron capture, emitting multiple characteristic gamma emissions. The capability to accurately quantify Ba-133 is of importance due to its persistence in the environment. This is enabled by its relatively long half-life and its uptake into the food chain due to its similarity in chemical properties to calcium. Therefore, screening for contamination of calcium-rich foodstuffs such as milk and milk powders, is required following a nuclear or radioactive contamination event. Refining a capability to quantify Ba-138 utilising gamma-ray spectrometry is advantageous due to its requirement of minimal sample preparation and usefulness in screening for a wide range of other radionuclides, therefore providing critical information in a relatively timely manner. in the 2017 IAEA ALMERA proficiency test exercise ANSTO’s Radioanalytical Chemistry Capability group demonstrated its proficiency in quantifying Ba-138 in water, and in quantifying other nuclides such as Cs-187 and Sr-90 in milk powder. However, the activity concentration of Ba-188 in the milk powder matrix was lower than the target value. Therefore, a study was undertaken to optimise a method for accurately quantifying Ba-138 in milk powder by gamma-ray spectrometry, holistically investigating the entire process from sample receipt and storage to counting geometry and interpretation of data. A series of storage and drying experiments were undertaken to optimise a method for determining the moisture content of a variety of supermarket bought milk powders, comparing measured mass changes using both desiccator and benchtop cooling following oven-drying. The impact of storage following unsealing the received sample container on moisture content was investigated and its implications on subsequent internal and cross-laboratory analysis were explored. The milk powders were packed into various geometries and analysed by gamma-ray spectrometry to quantify the naturally-occurring radionuclides present in the milk powder. This data was used to better understand the matrix and investigate the possible interference of naturally-occurring radionuclides in the quantification of Ba-188. Milk powders were also purposefully spiked with known activities of Ba-133 and a comparison of various counting geometries, the impact of sample density and self-absorption on counting efficiency were investigated. The use of a variety of calibration standards of varying geometries and densities was also explored to assess their applicability to the milk powder matrix. This paper will detail the investigation findings and propose recommendations for a more reliable method for the quantification of Ba-133 in milk powder by gamma-ray spectrometry to be hence employed in ANSTO’s Radioanalytical Chemistry Capability laboratory.
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    Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation
    (Springer Link, 2015-01) Callaghan, PD; Wimberley, CA; Rahardjo, GL; Berghofer, PJ; Pham, TQ; Jackson, TW; Zahra, D; Bourdier, T; Wyatt, N; Greguric, ID; Howell, NR; Siegele, R; Pastuovic, Z; Mattner, F; Loc'h, C; Grégoire, MC; Katsifis, A
    The in vivo binding parameters of the novel imidazopyridine TSPO ligand [18F]PBR102 were assessed and compared with those of [18F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). Methods Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [18F]PBR102 or [18F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration–time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [125I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. Results The BPs of [18F]PBR102 [18F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [11C]PK11195. The presaturation study showed differences in the volume of distribution between the ipsilateral striatum and the striatum contralateral to the injury (0.7) indicating that an assumption of the SRTM was not met. The modelling indicated that the BPs were consistent for both ligands. Between the SRTM and 2TC model, the BPs were highly correlated, but there was a bias in BP. Conclusion [18F]PBR102 and [18F]PBR111 have equivalent binding properties in vivo, displaying significantly greater BPs with lower signal-to-noise ratio than [11C]PK11195. While an assumption of the SRTM was not met, this modelling approach was validated against 2TC modelling for both ligands, facilitating future use in longitudinal PET imaging of neuroinflammation.© 2014, Springer Nature
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    Development of the Australian standard for germanium-68 by two liquid scintillation counting methods
    (Elsevier B. V., 2018-04) van Wyngaardt, WM; Smith, ML; Jackson, TW; Howe, B; Tobin, SM; Reinhard, MI
    In response to the increasing application of 68Ge/68Ga and 68Ga in nuclear medicine, an international comparison of activity measurement of 68Ge in equilibrium with 68Ga was organised. ANSTO standardised the comparison solution by the 4π(LS)β+-γ coincidence extrapolation and TDCR efficiency calculation methods, with excellent agreement between the two results. The primary standard was transferred to the ANSTO Secondary Standard Ionisation Chamber. Internationally traceable Australian Certified Reference Materials (ACRMs) of 68Ge/68Ga can now be prepared in various measurement geometries applied in nuclear medicine. © 2017 Crown Copyright, Published by Elsevier Ltd. All
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    Evidence against solar influence on nuclear decay constants
    (Elsevier B. V., 2016-10-10) Pommé, S; Stroh, H; Paepen, J; Van Ammel, R; Marouli, M; Altzitzoglou, T; Hult, M; Kossert, K; Nähle, O; Schrader, H; Juget, F; Bailat, CJ; Nedjadi, Y; Bochud, F; Buchillier, T; Michotte, C; Courte, S; van Rooy, MW; van Staden, MJ; Lubbe, J; Simpson, BRS; Fazio, A; De Felice, P; Jackson, TW; van Wyngaardt, WM; Reinhard, MI; Golya, J; Bourke, S; Roy, T; Galea, R; Keightley, JD; Ferreira, KM; Collins, SM; Ceccatelli, A; Unterweger, MP; Fitzgerald, R; Bergeron, DE; Pibida, L; Verheyen, L; Bruggeman, M; Vodenik, B; Korun, M; Chisté, V; Amiot, MN
    The hypothesis that proximity to the Sun causes variation of decay constants at permille level has been tested and disproved. Repeated activity measurements of mono-radionuclide sources were performed over periods from 200 days up to four decades at 14 laboratories across the globe. Residuals from the exponential nuclear decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ from one data set to another and are attributable to instabilities in the instrumentation and measurement conditions. The most stable activity measurements of alpha, beta-minus, electron capture, and beta-plus decaying sources set an upper limit of 0.0006% to 0.008% to the amplitude of annual oscillations in the decay rate. Oscillations in phase with Earth's orbital distance to the Sun could not be observed within a to range of precision. There are also no apparent modulations over periods of weeks or months. Consequently, there is no indication of a natural impediment against sub-permille accuracy in half-life determinations, renormalisation of activity to a distant reference date, application of nuclear dating for archaeology, geo- and cosmochronology, nor in establishing the SI unit becquerel and seeking international equivalence of activity standards. © 2016 The Authors. Published by Elsevier B.V.
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    Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-L-tyrosine on the TracerLab FXFN module
    (Elsevier B.V., 2011-07-01) Bourdier, T; Greguric, ID; Roselt, P; Jackson, TW; Faragalla, J; Katsifis, A
    Introduction: An efficient fully automated method for the radiosynthesis of enantiomerically pure O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) using the GE TracerLab FXFN synthesis module via the O-(2-tosyloxyethyl)-N-trityl-L-tyrosine tert-butylester precursor has been developed. Methods: The radiolabelling of [18F]FET involved a classical [18F]fluoride nucleophilic substitution performed in acetonitrile using potassium carbonate and Kryptofix 222, followed by acid hydrolysis using 2N hydrochloric acid. Results: [18F]FET was produced in 35±5% (n=22) yield non-decay-corrected (55±5% decay-corrected) and with radiochemical and enantiomeric purity of >99% with a specific activity of >90 GBq/μmol after 63 min of radiosynthesis including HPLC purification and formulation. Conclusion: The automated radiosynthesis provides high and reproducible yields suitable for routine clinical use. © 2011 Elsevier Inc.
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    Influence of metal ions on the Ga-68-labeling of dotatate
    (Elsevier, 2013-12-01) Oehlke, E; Le, VS; Lengkeek, NA; Pellegrini, PA; Jackson, TW; Greguric, ID; Weiner, R
    The influence of metal cations (Fe3+, Fe2+, In3+, Cu2+, Ca2+, Al3+, Co2+, Lu3+, Ni2+, Pb2+, Ti4+, Y3+, Yb3+, Zn2+, and Zr4+) on the radiolabeling yield of [68Ga(DOTATATE)] was evaluated. Our most important observation was that, within our experimental limit, the metal ion/ligand ratio plays a critical role on the influence of most metal ions. More in-depth studies, with Cu2+ and Fe3+, revealed that reaction temperature and concentration changes have little effect, but speciation changes with pH are crucial. Furthermore, we found that [68Ga(DOTATATE)] is stable in the presence of high concentrations of Fe3+, Zn2+ and Pb2+, but transmetalates with Cu2+ at 95 °C. © 2013, Elsevier Ltd.
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    On decay constants and orbital distance to the Sun—part I: alpha decay
    (IOP Publishing, 2016-11-28) Pommé, S; Stroh, H; Paepen, J; Van Ammel, R; Marouli, M; Altzitzoglou, A; Hult, M; Kossert, K; Nähle, O; Schrader, H; Juget, F; Bailat, C; Nedjadi, Y; Bochud, F; Buchillier, T; Michotte, M; Courte, S; van Rooy, MW; van Staden, MJ; Lubbe, L; Simpson, BRS; Fazio, A; De Felice, D; Jackson, TW; van Wyngaardt, WM; Reinhard, MI; Golya, J; Bourke, S; Roy, T; Galea, R; Keightley, JD; Ferreira, KM; Collins, SM; Ceccatelli, A; Verheyen, L; Bruggeman, M; Vodenik, M; Korun, M; Chisté, V; Amiot, MN
    Claims that proximity to the Sun causes variation of decay constants at permille level have been investigated for alpha decaying nuclides. Repeated decay rate measurements of 209Po, 226Ra, 228Th, 230U, and 241Am sources were performed over periods of 200 d up to two decades at various nuclear metrology institutes around the globe. Residuals from the exponential decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ in amplitude and phase from one data set to another and appear attributable to instabilities in the instrumentation and measurement conditions. The most stable activity measurements of α decaying sources set an upper limit between 0.0006% and 0.006% to the amplitude of annual oscillations in the decay rate. There are no apparent indications for systematic oscillations at a level of weeks or months. Oscillations in phase with Earth's orbital distance to the sun could not be observed within 10−5–10−6 range precision. © The Authors CC BY 3.0 licence
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    On decay constants and orbital distance to the Sun—part II: beta minus decay
    (IOP Publishing, 2016-11-28) Pommé, S; Stroh, H; Paepen, J; Van Ammel, R; Marouli, M; Altzitzoglou, A; Hult, M; Kossert, K; Nähle, O; Schrader, H; Juget, F; Bailat, C; Nedjadi, Y; Bochud, F; Buchillier, T; Michotte, M; Courte, S; van Rooy, MW; van Staden, MJ; Lubbe, L; Simpson, BRS; Fazio, A; De Felice, D; Jackson, TW; van Wyngaardt, WM; Reinhard, MI; Golya, J; Bourke, S; Roy, T; Galea, R; Keightley, JD; Ferreira, KM; Collins, SM; Ceccatelli, A; Verheyen, L; Bruggeman, M; Vodenik, M; Korun, M; Chisté, V; Amiot, MN
    Claims that proximity to the Sun causes variations of decay constants at the permille level have been investigated for beta-minus decaying nuclides. Repeated activity measurements of 3H, 14C, 60Co, 85Kr, 90Sr, 124Sb, 134Cs, 137Cs, and 154Eu sources were performed over periods of 259 d up to 5 decades at various nuclear metrology institutes. Residuals from the exponential decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ in amplitude and phase from one data set to another and appear attributable to instabilities in the instrumentation and measurement conditions. Oscillations in phase with Earth's orbital distance to the Sun could not be observed within 10−4–10−5 range precision. The most stable activity measurements of β− decaying sources set an upper limit of 0.003%–0.007% to the amplitude of annual oscillations in the decay rate. There are no apparent indications for systematic oscillations at a level of weeks or months. © The Authors CC BY 3.0 licence
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    On decay constants and orbital distance to the Sun—part III: beta plus and electron capture decay
    (IOP Publishing, 2016-11-28) Pommé, S; Stroh, H; Paepen, J; Van Ammel, R; Marouli, M; Altzitzoglou, T; Hult, M; Kossert, K; Nähle, O; Schrader, H; Juget, F; Bailat, C; Nedjadi, Y; Bochud, F; Buchillier, T; Michotte, C; Courte, S; van Rooy, MW; van Staden, MJ; Lubbe, J; Simpson, BRS; Fazio, A; De Felice, P; Jackson, TW; van Wyngaardt, WM; Reinhard, MI; Golya, J; Bourke, S; Roy, T; Galea, R; Keightley, JD; Ferreira, KM; Collins, SM; Ceccatelli, A; Verheyen, L; Bruggeman, M; Vodenik, B; Korun, M; Chisté, V; Amiot, MN
    The hypothesis that seasonal changes in proximity to the Sun cause variation of decay constants at permille level has been tested for radionuclides disintegrating through electron capture and beta plus decay. Activity measurements of 22Na, 54Mn, 55Fe, 57Co, 65Zn, 82+85Sr, 90Sr, 109Cd, 124Sb, 133Ba, 152Eu, and 207Bi sources were repeated over periods from 200 d up to more than four decades at 14 laboratories across the globe. Residuals from the exponential nuclear decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ from one data set to another and appear attributable to instabilities in the instrumentation and measurement conditions. Oscillations in phase with Earth's orbital distance to the sun could not be observed within 10−4–10−5 range precision. The most stable activity measurements of β+ and EC decaying sources set an upper limit of 0.006% or less to the amplitude of annual oscillations in the decay rate. There are no apparent indications for systematic oscillations at a level of weeks or months. © The Authors CC BY 3.0 licence
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    Plasmonic light yield enhancement of a liquid scintillator
    (AIP Publishing LLC, 2013-05-28) Bignell, LJ; Mume, E; Jackson, TW; Lee, GP
    We demonstrate modifications to the light yield properties of an organic liquid scintillator due to the localization of the tertiary fluorophore component to the surface of Ag-core silica-shell nanoparticles. We attribute this enhancement to the near-field interaction of Ag nanoparticle plasmons with these fluor molecules. The scintillation light yield enhancement is shown to be equal to the fluorescence enhancement within measurement uncertainties. With a suitable choice of plasmon energy and scintillation fluor, this effect may be used to engineer scintillators with enhanced light yields for radiation detection applications. © 2013, AIP Publishing LLC.
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    Primary standardisation of technetium-99m by liquid scintillation coincidence counting
    (Elsevier B. V., 2020-02) van Wyngaardt, WM; Tobin, SM; Lee, S; Smith, ML; Jackson, TW; Ilter, J; Howe, B; Sarbutt, A
    Technetium-99m was standardised by the 4π(LS)ce-γ coincidence extrapolation method. Sensitivity of the 4π(LS) channel to two types of radiation, namely conversion electrons and γ-rays, resulted in incorrect activity values being obtained when this was not adequately accounted for. Measurements were more robust when the LS detection efficiency was optimised, and when a γ-window setting was used that monitored the combined LS efficiency for conversion electrons and γ-rays. The primary standard was internationally compared through participation in the BIPM.RI(II)-K4.Tc99m key comparison. © 2019 Elsevier Ltd
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    Radiosynthesis and biological evaluation of L and D S-(3-[18F]Fluoropropyl)-homocysteine for tumor imaging using positron emission tomography
    (Americam Chemical Society, 2011-03-24) Bourdier, T; Shepherd, R; Berghofer, PJ; Jackson, TW; Fookes, CJR; Denoyer, D; Dorow, DS; Greguric, ID; Grégoire, MC; Hicks, RJ; Katsifis, A
    Interest in radiolabeled amino acids for metabolic imaging of cancer and limitations with [11C]methionine has prompted the development of a new 18F-labeled methionine derivative S-(3-[18F]fluoropropyl)homocysteine ([18F]FPHCys). The L and D enantiomers of [18F]FPHCys were prepared from their respective protected S-(3-tosyloxypropyl)homocysteine precursors 1 by [18F]fluoride substitution using K2.2.2 and potassium oxalate, followed by acid hydrolysis on a Tracerlab FXFN synthesis module. [18F]-L-FPHCys and [18F]-D-FPHCys were isolated in 20 ( 5% radiochemical yield and >98% radiochemical and enantiomeric purity in 65 min. Competitive uptake studies in A375 and HT29 tumor cells suggest that L- and D-[18F]FPHCys are taken up by the L-transporter system. [18F]-L-FPHCys and [18F]-D-FPHCys displayed good stability In Vivo without incorporation into protein at least 2 h postinjection. Biodistribution studies demonstrate good uptake in A375 tumor-bearing rodents with tumor to blood ratios of 3.5 and 5.0 for [18F]-L-FPHCys and [18F]-D-FPHCys, respectively, at 2 h postinjection. © 2011, American Chemical Society.
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    Radiosynthesis, in vivo biological evaluation, and imaging of brain lesions with [123I]-CLINME, a new SPECT tracer for the translocator protein
    (Hindawi Publishing Corporation, 2015-06-25) Mattner, F; Quinlivan, M; Greguric, ID; Pham, TQ; Liu, X; Jackson, TW; Berghofer, PJ; Fookes, CJR; Dikic, B; Grégoire, MC; Dollé, F; Katsifis, A
    The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4′-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [123I]-CLINME was prepared in 70–80% radiochemical yield. The uptake of [123I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [123I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [123I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [123I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion : nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [123I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT. © 2015 F. Mattner et al.
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    Results of an international comparison of activity measurements of 68Ge
    (Elsevier B. V., 2018-04) Cessna, JT; Fitzgerald, R; Zimmerman, BE; Laureano-Pérez, L; Bergeron, DE; van Wyngaardt, WM; Smith, ML; Jackson, TW; Howe, B; da Silva, CJ; Iwahara, A; da Cruz, PAL; Zhang, M; Liu, H; Liang, JC; Fréchou, C; Bobin, C; Cassette, P; Kossert, K; Nähle, O; Marganiec-Gałązka, J; Joseph, L; Ravindra, A; Kulkarni, DN; Yunoki, A; Sato, Y; Lee, KB; Lee, JM; Agusbudiman, A; Dziel, T; Listkowska, A; Tymiński, Z; Sahagia, M; Antohe, A; Ioan, MR; Luca, A; Krivosek, M; Ometakova, J; Javornik, A; Zalesakova, M; García-Toraño Martinez, E; Roteta, M; Mejuto, M; Nedjadi, Y; Juget, F; Yuan, MC; Yeh, CY; Yeltepe, E; Dirican, A; Keightley, JD; Pearce, AK
    An international key comparison, identifier CCRI(II)-K2.Ge-68, has been performed. The National Institute of Standards and Technology (NIST) served as the pilot laboratory, distributing aliquots of a 68Ge/68Ga solution. Results for the activity concentration, CA, of 68Ge at a reference date of 12h00 UTC 14 November 2014 were submitted by 17 laboratories, encompassing many variants of coincidence methods and liquid-scintillation counting methods. The first use of 4π(Cherenkov)β-γ coincidence and anticoincidence methods in an international comparison is reported. One participant reported results by secondary methods only. Two results, both utilizing pure liquid-scintillation methods, were identified as outliers. Evaluation using the Power-Moderated Mean method results in a proposed Comparison Reference Value (CRV) of 621.7(11) kBq g−1, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6 mL ampoules to the BIPM to link the comparison to the International Reference System (SIR) which may lead to the evaluation of a Key Comparison Reference Value and associated degrees of equivalence. An international key comparison, identifier CCRI(II)-K2.Ge-68, has been performed. The National Institute of Standards and Technology (NIST) served as the pilot laboratory, distributing aliquots of a 68Ge/68Ga solution. Results for the activity concentration, CA, of 68Ge at a reference date of 12h00 UTC 14 November 2014 were submitted by 17 laboratories, encompassing many variants of coincidence methods and liquid-scintillation counting methods. The first use of 4π(Cherenkov)β-γ coincidence and anticoincidence methods in an international comparison is reported. One participant reported results by secondary methods only. Two results, both utilizing pure liquid-scintillation methods, were identified as outliers. Evaluation using the Power-Moderated Mean method results in a proposed Comparison Reference Value (CRV) of 621.7(11) kBq g−1, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6 mL ampoules to the BIPM to link the comparison to the International Reference System (SIR) which may lead to the evaluation of a Key Comparison Reference Value and associated degrees of equivalence. An international key comparison, identifier CCRI(II)-K2.Ge-68, has been performed. The National Institute of Standards and Technology (NIST) served as the pilot laboratory, distributing aliquots of a 68Ge/68Ga solution. Results for the activity concentration, CA, of 68Ge at a reference date of 12h00 UTC 14 November 2014 were submitted by 17 laboratories, encompassing many variants of coincidence methods and liquid-scintillation counting methods. The first use of 4π(Cherenkov)β-γ coincidence and anticoincidence methods in an international comparison is reported. One participant reported results by secondary methods only. Two results, both utilizing pure liquid-scintillation methods, were identified as outliers. Evaluation using the Power-Moderated Mean method results in a proposed Comparison Reference Value (CRV) of 621.7(11) kBq g−1, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6 mL ampoules to the BIPM to link the comparison to the International Reference System (SIR) which may lead to the evaluation of a Key Comparison Reference Value and associated degrees of equivalence. © 2021 Elsevier Ltd.
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    Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma
    (American Chemical Society, 2007-07-26) Pham, TQ; Greguric, ID; Liu, X; Berghofer, PJ; Ballantyne, P; Chapman, J; Mattner, F; Dikic, B; Jackson, TW; Loc'h, C; Katsifis, A
    The imaging potential of a series of [123I]benzamides was studied in mice bearing B16F0 melanoma tumors. Compound [123I]25 exhibited tumor uptake >8 %ID/g at 1 h, while that of [123I]14d and [123I]25 reached a maximum of 9−12 %ID/g at 6 h. Standardized uptake values of [123I]14d were higher than 100 between 24 and 72 h after injection. In haloperidol treated animals, the tumor uptake of [123I]14d was not significantly different to controls, while significant reduction of [123I]25 uptake was observed, supporting that [123I]14d uptake relates to melanin interaction, whereas part of the mechanism of [123I]25 uptake is related to its σ1-receptor affinity. Benzamides 14d and 25, which display rapid and high tumor uptake, appear to be promising imaging agents for melanoma detection, while 14d, which displays a long lasting and high melanoma/nontarget ratio, is more suitable for evaluation as a potential radiotherapeutic. © 2007, American Chemical Society.