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Browsing by Author "Arthur, A"

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Fluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111
(John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BH
Objectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
In vivo PET imaging with [18F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes
(Springer Nature, 2016-05-18) Cochran, BJ; Ryder, WJ; Parmar, A; Tang, S; Reilhac, A; Arthur, A; Charil, A; Hamze, H; Barter, PJ; Kritharides, L; Meikle, SR; Grégoire, MC; Rye, KA
Type 2 diabetes is characterised by decreased HDL levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDLs. Pharmacological elevation of HDL and apoA-I levels is associated with improved glycaemic control in patients with type 2 diabetes. This is partly due to improved glucose uptake in skeletal muscle.© 2016 Springer Nature
Quantification of dopamine d2 receptor density and apparent affinity can be used to longitudinally assess transient striatal variations during adolescence using [11c]raclopride pet imaging
(John Wiley & Sons, Inc., 2017-04-11) Callaghan, PD; Sobbi, PF; Safavi-Naeini, M; Wimberley, CA; Davis, E; Zahra, D; Arthur, A; Rahardjo, GL; Perkins, G; Pascali, G; Reilhac-Laborde, A; Grégoire, MC
Background Transient increases in striatal dopamine D2 receptors occur during adolescence in rats, correlating with a developmental epoch where synaptic pruning occurs. Alteration of these processes with external stresses during adolescence may lead to affective disorders later in life. Longitudinal PET imaging with [11C]raclopride using a partial saturation design allows assessment of density (Bavail) and affinity changes (appKd) to map neurodevelopmental changes in D2 expression, which necessitates a significant level of receptors occupancy during the PET study. Aims Validate that repeated transient partial saturation of D2 receptors does not bias measures of D2 Bavail and appKd assessed using PET/CT imaging with [11C]raclopride. Methods Three cohorts of male Sprague-Dawley rats (n=6-7/group) underwent a single session of PET/CT imaging (INVEON, Siemens, USA) with [11C]raclopride (5 nmol injected i.v.) as naïve or after repeated partial saturation of D2 receptors: Cohort A received 5nmol raclopride (i.v) weekly from PND35 (postnatal day) to PND96 with PET imaging session at PND96, cohort B was scanned at PND96; Cohort C was scanned at PND35 Datasets were reconstructed (2D-FBP), coregistered with CT and time-activity data extracted using age matched atlas-based volumes of interest (striatum, cerebellum). in vivo receptor density and appKd were derived using kinetic modelling (comparisons used 1-way ANOVA follow by post hoc test). Results Expected differences in Bavail and appKd were seen between the adolescent (PND35) and the adult (PND96) cohorts, corresponding with increases in D2 receptor consistently reported in the literature using post mortem methods. No significant difference was observed in both Bavail and appKd in cohort A, exposed to repeated D2 partial saturation, compared to the naïve cohort B. Conclusion Longitudinal quantification of dopamine D2 receptor density and apparent affinity in vivo using [11C]raclopride PET imaging with partial saturation can be used to map changes in adolescent and adult rats.
Selective, high-contrast detection of syngeneic glioblastoma in vivo
(Springer Nature, 2020-06-19) Banati, RB; Wilcox, P; Xu, R; Yin, G; Si, E; Son, ET; Shimizu, M; Holsinger, RMD; Parmar, A; Zahra, D; Arthur, A; Middleton, RJ; Liu, GJ; Charil, A; Graeber, MB
Glioblastoma is a highly malignant, largely therapy-resistant brain tumour. Deep infiltration of brain tissue by neoplastic cells represents the key problem of diffuse glioma. Much current research focuses on the molecular makeup of the visible tumour mass rather than the cellular interactions in the surrounding brain tissue infiltrated by the invasive glioma cells that cause the tumour’s ultimately lethal outcome. Diagnostic neuroimaging that enables the direct in vivo observation of the tumour infiltration zone and the local host tissue responses at a preclinical stage are important for the development of more effective glioma treatments. Here, we report an animal model that allows high-contrast imaging of wild-type glioma cells by positron emission tomography (PET) using [18 F]PBR111, a selective radioligand for the mitochondrial 18 kDa Translocator Protein (TSPO), in the Tspo−/− mouse strain (C57BL/6-Tspotm1GuMu(GuwiyangWurra)). The high selectivity of [18 F]PBR111 for the TSPO combined with the exclusive expression of TSPO in glioma cells infiltrating into null-background host tissue free of any TSPO expression, makes it possible, for the first time, to unequivocally and with uniquely high biological contrast identify peri-tumoral glioma cell invasion at preclinical stages in vivo. Comparison of the in vivo imaging signal from wild-type glioma cells in a null background with the signal in a wild-type host tissue, where the tumour induces the expected TSPO expression in the host’s glial cells, illustrates the substantial extent of the peritumoral host response to the growing tumour. The syngeneic tumour (TSPO+/+) in null background (TSPO−/−) model is thus well suited to study the interaction of the tumour front with the peri-tumoral tissue, and the experimental evaluation of new therapeutic approaches targeting the invasive behaviour of glioblastoma. © 2020, The Author(s).
Simultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation
(IOP science publishing, 2016-01-21) Reilhac, A; Boisson, F; Wimberley, CA; Parmar, A; Zahra, D; Hamze, H; Davis, E; Arthur, A; Bouillot, C; Charil, A; Grégoire, MC
In PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies. © 2016 Institute of Physics and Engineering in Medicine
Synthesis and biological characterisation of 18F-SIG343 and 18F-SIG353, novel and high selectivity σ2 radiotracers, for tumour imaging properties
(Springer Nature, 2013-12-11) Nguyen, VH; Pham, TQ; Fookes, CJR; Berghofer, PJ; Greguric, I; Arthur, A; Mattner, F; Rahardjo, GL; Davis, E; Howell, NR; Grégoire, MC; Katsifis, A; Shepherd, R
Sigma2 (σ2) receptors are highly expressed in cancer cell lines and in tumours. Two novel selective 18F-phthalimido σ2 ligands, 18F-SIG343 and 18F-SIG353, were prepared and characterised for their potential tumour imaging properties. © 2013 Nguyen et al.; licensee Springer.
Test-retest reliability and inter scanner variability of 11C-raclopride striatal binding potentials between two INVEON PET/CT imaging systems for naïve Sprague Dawley rats
(Wiley, 2014-04-16) Callaghan, PD; Zahra, D; Wimberley, CA; Arthur, A; Rahardjo, GL; Hamze, H; Davis, E; Nguyen, A; Boisson, F; Perkins, G; Pascali, G; Reilhac, A; Grégoire, MC
Background: 11C-raclopride is a routine tracer for quantification of dopamine D2 receptors in neurological and psychiatric disease. D2 imaging in key longitudinal models has significant utility of understanding mechanisms and therapeutic interventions. Aims: Optimisation of preclinical imaging and data analysis protocols for 11C-raclopride in rat brain. Methods: a) Test-retest reliability: Naïve male Sprague Dawley rats (n = 6) underwent test-retest assessment of binding potential variability, with two scans, 1 week apart. Rats were anaesthetised (1–5% isoflurane) and received 11C-raclopride (>0.1 nmol, 20–40 MBq) during 1 hour image acquisition (Siemens Inveon PET/CT), followed by a 10 minute CT scan. b) Assessment of the intersystem variability of the INVEON scanners (n = 12). Test-retest experiments were performed on a second INVEON system. c) Assessment of inter system variability with arterial blood sampling (n = 5). Acquisitions were performed (as above) with prior femoral artery cannulation: 23 blood samples (∼30 ul) were collected during PET acquisition, and plasma metabolite corrected input functions generated. PET list mode data were histogrammed (23 frames) and reconstructed with 2D filtered backprojection algorithm. The impact of some post-reconstruction image processing techniques, such iterative deconvolution of the image and data denoising techniques, onto the accuracy and reliability of the computed parameter of interest were also investigated. Binding potential parametric maps were calculated from the dynamic PET data (using either a standard reference tissue modelling using the cerebellum TAC (test-retest), and or a 2 compartment kinetic modelling with input function). Preliminary results: Significant improvements were seen for tissue activity data after denoising /iterative deconvolution (see figure). Analysis of binding potential data are currently in progress. Conclusion: Assessment of within and intersystem variability will aid the appropriate statistical design of future longitudinal 11C-raclopride imaging studies. Improvements from post-reconstruction image processing techniques show significant benefits. © 1999-2022 John Wiley & Sons, Inc.

Browsing by Author "Arthur, A"

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