Browsing by Author "Bourdier, T"

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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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    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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    Discovery of [F-18]N-(2-(Diethylamino)ethyl)-6-fluoronicotinamide: a melanoma positron emission tomography imaging radiotracer with high tumor to body contrast ratio and rapid renal clearance
    (American Chemical Society, 2009-09-10) Greguric, ID; Taylor, SR; Denoyer, D; Ballantyne, P; Berghofer, PJ; Roselt, P; Pham, TQ; Mattner, F; Bourdier, T; Neels, OC; Dorow, DS; Loc'h, C; Hicks, RJ; Katsifis, A
    The high melanoma uptake and rapid body clearance displayed by our series of [123I]iodonicotinamides prompted the development of [18F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide ([18F]2), a novel radiotracer for PET melanoma imaging. Significantly, unlike fluorobenzoates, [18F]fluorine incorporation on the nicotinamide ring is one step, facile, and high yielding. [18F]2 displayed high tumor uptake, rapid body clearance via predominantly renal excretion, and is currently being evaluated in preclinical studies for progression into clinical trials to assess the responsiveness of therapeutic agents. © 2009, American Chemical Society
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    Evaluation of the PBR ligand [123I]CLINDE in an animal model of experimental autoimmune encephalomyelitis
    (Australasian Quaternary Association, 2008-05-01) Mattner, F; Linares, D; Staykova, M; Grégoire, MC; Pham, TQ; Bourdier, T; Quinlivan, M; Callaghan, PD; Willenborg, DO; Katsifis, A
    Objectives: The aim of this study was to evaluate the Peripheral Benzodiazepine Receptor (PBR) radioligand [123I]CLINDE in the rat inflammatory disease model of Experimental Autoimmune Encephalomyelitis (EAE). Methods: EAE was induced with blast cells collected from spleen and lymph nodes of Lewis rats induced with myelin basic protein and complete Freund's adjuvant. Biodistribution with [123I]CLINDE was undertaken on EAE rats exhibiting different disease severity and compared to controls.The relationship between inflammatory lesions and tracer uptake was investigated using ex vivo autoradiography and immunohistochemistry. Results: Disease severity was confirmed by histopathology in spinal cord. Results indicate enhanced uptake of [123I]CLINDE in all animals induced with EAE compared to controls. This uptake reflected the ascending nature of the inflammatory lesions ie. uptake in the lumbar spinal cord > thoracic cord > cervical cord > medulla > cerebellum. Uptake of [123I]CLINDE in the lumbar and thoracic cord correlated with disease severity. A 2 and 3 fold enhancement in PBR expression was observed in the brain and spinal cord of animals with a clinical score of 3 compared to controls. Regional [123I]CLINDE uptake closely correlated with localisation of PBR, shown using autoradiography and immunohistochemisty. Conclusions: These results demonstrate the ability of [123I]CLINDE to measure in vivo changes of PBR density according to area of involvement and the severity of disease suggesting it as a potential SPECT tracer for the study of inflammation and multiple sclerosis. © 2022 Journal of Nuclear Medicine
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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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    Preclinical characterization of 18FD-FPHCys, a new amino acid-based PET tracer
    (Springer, 2012-04-01) Denoyer, D; Kirby, L; Waldeck, K; Roselt, P; Neels, OC; Bourdier, T; Shepherd, R; Katsifis, A; Hicks, RJ
    The imaging potential of a new F-18-labelled methionine derivative, S-(3-[F-18]fluoropropyl)-d-homocysteine (F-18-D-FPHCys), and its selectivity for amino acid transporter subtypes were investigated in vitro and by imaging of human tumour xenografts. Expression of members of the system L (LAT isoforms 1-4 and 4F2hc) and ASCT (ASCT isoforms 1 and 2) amino acid transporter subclasses were assessed by quantitative real-time PCR in four human tumour models, including A431 squamous cell carcinoma, PC3 prostate cancer, and Colo 205 and HT-29 colorectal cancer lines. The first investigations for the characterization of F-18-D-FPHCys were in vitro uptake studies by comparing it with [1-C-14]-l-methionine (C-14-MET) and in vivo by PET imaging. In addition, the specific involvement of LAT1 transporters in F-18-D-FPHCys accumulation was tested by silencing LAT1 mRNA transcription with siRNAs. To determine the proliferative activity in tumour xenografts ex vivo, Ki-67 staining was used as a biomarker. A431 cells showed the highest F-18-D-FPHCys uptake in vitro and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention was observed with C-14-MET. F-18-D-FPHCys retention was strongly correlated with LAT1 expression both in vitro (R (2) = 0.85) and in vivo (R (2) = 0.99). Downregulation of LAT1 by siRNA inhibited F-18-D-FPHCys uptake, demonstrating a clear dependence on this transporter for tumour uptake. Furthermore, F-18-D-FPHCys accumulation mirrored cellular proliferation. The favourable properties of F-18-D-FPHCys make this tracer a promising imaging probe for detection of tumours as well as for the noninvasive evaluation and monitoring of tumour growth.© 2012, Springer.
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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 of a novel PET fluoronicotinamide for melanoma tumour PET imaging [18F]MEL050
    (CSIRO Publishing, 2011-01-01) Greguric, ID; Taylor, S; Pham, TQ; Wyatt, NA; Jiang, CD; Bourdier, T; Loc'h, C; Roselt, P; Neels, OC; Katsifis, A
    [18F]6-Fluoro-N-[2-(diethylamino)ethyl]nicotinamide [18F]MEL050 is a novel nicotinamide-based radiotracer, designed to target random metastatic dissemination of melanoma tumours by targeting melanin. Preclinical studies suggest that [18F]MEL050 has an excellent potential to improve diagnosis and staging of melanoma. Here we report the radiochemical optimization conditions of [18F]MEL050 and its large scale automated synthesis using a GE FXFN automated radiosynthesis module for clinical, phase-1 investigation. [18F]MEL050 was prepared via a one-step synthesis using no-carrier added K[18F]F-Krytpofix® 222 (DMSO, 170°C, 5 min) followed by HPLC purification. Using 6-chloro-N-[2-(diethylamino)ethyl]nicotinamide as precursor, [18F]MEL050 was obtained in 40–46% radiochemical yield (non-decay corrected), in greater than 99.9% radiochemical purity and specific activity ranging from 240 to 325 GBq μmol–1. Total synthesis time including formulation was 40 min and [18F]MEL050 was stable (99.8%) in PBS for 6 h. © 2011, CSIRO Publishing
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    A rapid solid-phase extraction method for measurement of non-metabolised peripheral benzodiazepine receptor ligands, [18F]PBR102 and [18F]PBR111, in rat and primate plasma
    (Elsevier, 2011-01) Katsifis, A; Loc'h, C; Henderson, D; Bourdier, T; Pham, TQ; Greguric, ID; Lam, P; Callaghan, PD; Mattner, F; Eberl, S; Fulham, MJ
    To develop a rapid and reliable method for estimating non-metabolised PBR ligands fluoroethoxy ([18F]PBR102)- and fluoropropoxy ([18F]PBR111)-substituted 2-(6-chloro-2-phenyl)imidazo[1,2-a]pyridine-3-yl)-N,N-diethylacetamides in plasma. © 2011 Elsevier Inc.
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    Synthesis and radiosynthesis of a novel PET fluorobenzyl piperazine for melanoma tumour imaging; [18F]MEL054
    (CSIRO publishing, 2012-02-18) Taylor, SR; Roberts, MR; Wyatt, NA; Pham, TQ; Stark, D; Bourdier, T; Roselt, P; Katsifis, A; Greguric, ID
    2-{2-[4-(4-[18F]-Fluorobenzyl)piperazin-1-yl]-2-oxoethyl}isoindolin-1-one ([18F]MEL054), is a new potent indolinone-based melanin binder designed to target melanotic tumours. [18F]MEL054 was prepared by an automated two-step radiosynthesis, comprising of the preparation of 4-[18F]fluorobenzaldehyde from 4-formyl-N,N,N-trimethylanilinium triflate, followed by reductive alkylation with 2-(2-oxo-2-piperazin-1-ylethyl)isoindolin-1-one. 4-[18F]Fluorobenzaldehyde was prepared on a GE TRACERlab FXFN module in 68 ± 8 % radiochemical yield (RCY, non-decay corrected), purified by a Sep-Pak Plus C18 cartridge and eluted into the reactor of an in-house modified Nuclear Interface [18F]FDG synthesis module for the subsequent reductive alkylation reaction. HPLC purification produced [18F]MEL054 in a collected RCY of 34 ± 9 % (non-decay corrected), the total preparation time (including Sep-Pak Plus C18 and HPLC purification) did not exceed 105 min. The radiochemical purity of [18F]MEL054 was greater than 99 % with a specific radioactivity of 71–119 GBq μmol–1 and [18F]MEL054 remained stable in saline solution (>98 %) after 3 h. © 2013 CSIRO.
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    Synthesis and stability of S-(2-[18F]fluoroethyl)-L-homocysteine for potential tumour imaging
    (John Wiley and Sons, 2008-09-25) Bourdier, T; Fookes, CJR; Pham, TQ; Greguric, ID; Katsifis, A
    inThe F-18 labelled methionine derivative S-(2-[18F]fluoroethyl)-L-homocysteine ([18F]FEHCys) was prepared by a one-pot two-step synthesis via the protected S-(2-bromoethyl)-L-homocysteine 1 and S-(2-chloroethyl)-L-homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro-analogue (22% at 100°C in 30 min). However, [18F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. © 2008 John Wiley & Sons, Ltd.