References of "Bahri, Mohamed Ali"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailPharmacokinetic characterization of [18F]UCB-H PET radiopharmaceutical in the rat brain.
Becker, Guillaume ULg; Warnier, Corentin; Serrano Navacerrada, Maria Elisa ULg et al

in Molecular Pharmaceutics (in press)

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with ... [more ▼]

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with positron emission tomography (PET), allows the assessment of synaptic density in the living brain. The first-in-class fluorinated SV2A specific radioligand, [18F]UCB-H, is now available at high-activity through an efficient radiosynthesis compliant with the current good manufacturing practices (cGMP). We report here a non-invasive method to quantify [18F]UCB-H binding in rat brain with microPET. Validation study in rats confirmed the need of high enantiomeric purity to target SV2A in vivo. We demonstrated the reliability of a population-based input function to quantify SV2A in preclinical microPET setting. Finally, we investigated the in vivo metabolism of [18F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [18F]UCB-H microPET seems a promising tool for the assessment of the synaptic density in the rat brain, and opens the way for longitudinal follow-up in neurodegenerative diseases rodents’ models. [less ▲]

Detailed reference viewed: 19 (1 ULg)
Peer Reviewed
See detailSelf in Dementia
Antoine, Nicolas ULg; Genon, Sarah ULg; Bastin, Christine ULg et al

in Mishara; Corlett, P.; Fletcher, P. (Eds.) et al Phenomenological Neuropsychiatry, How Patient Experience Bridges Clinic with Clinical Neuroscience (in press)

Detailed reference viewed: 124 (28 ULg)
Full Text
Peer Reviewed
See detailRegiospecific radiolabelling of Nanofitin on Ni Magnetic Beads with [18F]FBEM and in vivo PET studies
Dammicco, Sylvestre ULg; Goux, Marine; Lemaire, Christian ULg et al

in Nuclear Medicine & Biology (2017)

Introduction: Nanofitins are low molecular weight, single chain and cysteine-free protein scaffolds able to selectively bind a defined biological target. They derive from Sac7d bacterial protein family ... [more ▼]

Introduction: Nanofitins are low molecular weight, single chain and cysteine-free protein scaffolds able to selectively bind a defined biological target. They derive from Sac7d bacterial protein family and are highly stable over a wide range of pH (0-13) and temperature (Tm ~80°C). Their extreme stability, low cost of production and high tolerability for chemical coupling make Nanofitins a very interesting alternative to antibodies and their fragments. Here, a hexahistidine tagged model Nanofitin (H4) directed against hen egg white lysozyme was radiolabelled and injected in mice to provide a baseline biodistribution and pharmacokinetic profiles to support future Nanofitin development programs. Method: A single cysteine residue has been genetically inserted in a model Nanofitin and its regioselective radiolabelling has been performed with 4-[18F]fluorobenzamido-N-ethylamino-maleimide ([18F]FBEM). The synthesis of [18F]FBEM has been completely implemented on a radiosynthesis unit (FastLab) including HPLC purification and formulation. Coupling with the [18F]FBEM has been achieved on a solid support (Ni magnetic beads) allowing rapid purification at room temperature without organic solvent. PET-MRI studies on C57BL/6 mice were conducted after injection of [18F]FBEM-Cys-H4 in order to access the biodistribution of this Nanofitin model. Results: Radiochemical yield (decay corrected) of 54±7% (n=4) was obtained after optimization for coupling the [18F]FBEM to Nanofitin. Pharmacokinetics results of [18F]FBEM-Cys-H4 revealed a fast clearance through the liver and the kidneys. Conclusion: An efficient new method on Ni magnetic beads was developed to radiolabelled his-tagged biomolecules with [18F]FBEM. This procedure was applied on a Nanofitin model Cys-H4 and biodistribution kinetic studies were achieved to evaluate the potential use of Nanofitin for diagnostic imaging. Fast clearance indicates that Nanofitins represent very interesting tools for diagnostic imaging. [less ▲]

Detailed reference viewed: 39 (10 ULg)
Peer Reviewed
See detailMean and variance of Dynamic Functional Connectivity in Parkinson’s Disease
Baquero Duarte, Katherine Andrea ULg; Guldenmund, Pieter; Rouillard, Maud ULg et al

Poster (2017, June 29)

Detailed reference viewed: 18 (4 ULg)
Full Text
Peer Reviewed
See detailComparative assessment of 6-[18F]fluoro-L-m-tyrosine and 6-[18F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson’s disease rat model.
Becker, Guillaume ULg; Bahri, Mohamed Ali ULg; Michel, Anne et al

in Journal of Neurochemistry (2017), 141

Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson’s disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical ... [more ▼]

Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson’s disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the pre-clinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [18F]fluoro-3,4-dihydroxyphenyl-L-alanine ([18F]FDOPA) and 6-[18F]fluoro-L-m-tyrosine ([18F]FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [18F]FMT and [18F]FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase (AADC) inhibitor. A catechol-O-methyl transferase inhibitor was also given before [18F]FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [18F]FMT and [18F]FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant Kc. However, only [18F]FMT Kc succeeded to discriminate between the partial and the full 6-OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [18F]FMT could be more sensitive, with respect of [18F]FDOPA, to investigate DA terminals loss in 6-OHDA rats, and open the way to in vivo AADC activity targeting in future investigations on progressive PD models. [less ▲]

Detailed reference viewed: 39 (8 ULg)
Full Text
Peer Reviewed
See detailRelating pessimistic memory predictions to Alzheimer’s disease brain structure
Genon, Sarah ULg; Simon, Jessica ULg; Bahri, Mohamed Ali ULg et al

Poster (2017, March 23)

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory ... [more ▼]

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory retrieval and investigated the neural correlates of pessimistic predictions for successfully retrieved memories in AD patients. AD patients and healthy older participants provided predictive judgements on their recognition performance before retrieval of famous (semantic) and recently learned (episodic) names. Correlations between grey matter volume (GMV) in T1 images and behavioural scores were examined with multivariate (PLS) and univariate (GLM) analyses in AD patients. AD patients showed a significant proportion of successful name recognition preceded by pessimistic prediction (Prediction_low_hits) in episodic memory. PLS revealed that behavioural pattern in AD patients was related with a mainly right lateralized pattern of GMV decrease including medial temporal lobe and posterior cingulate cortex, but also right ventrolateral prefrontal cortex (VLPFC). GLM further confirmed that pessimistic prediction negatively correlated with GMV in VLPFC. Thus, impaired monitoring processes (possibly influenced by inaccurate beliefs) allowing inferences about one’s own memory performance are primarily related to decrease GMV in VLPFC in AD patients. [less ▲]

Detailed reference viewed: 33 (2 ULg)
Full Text
See detailEvaluating the specificity of [18F] UCB-H for the isoform SV2A, compared with isoforms SV2B and SV2C
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017, February 01)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the epilepsy (1, 2). [18F]UCB-H was developed like a tool to study the role of this isoform with neuroimaging techniques (3, 4). The objective of this study was to evaluate its specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Data were expressed in Standard Uptake Value and then, the area under the curve was calculated for the total process. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy. [less ▲]

Detailed reference viewed: 27 (1 ULg)
Full Text
Peer Reviewed
See detailSedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.
KIRSCH, Murielle ULg; Guldenmund, Pieter; Bahri, Mohamed Ali ULg et al

in Anesthesia and Analgesia (2017), 124(2),

Detailed reference viewed: 59 (15 ULg)
Full Text
Peer Reviewed
See detailIN VIVO STUDY OF THE SV2A PROTEIN IN THE KAINIC ACID EPILEPSY RAT MODEL
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017)

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to study in vivo SV2A brain proteins [3, 4]. The present pilot study was undertaken to evaluate for the first time in vivo in rats SV2A expression in the Kaïnic Acid (KA) epilepsy model [5]. Although this model is well studied in mice, few reports were devoted to rats. Imaging-wise, rats are very interesting thanks to a bigger brain size (reduction of the partial volume effect). Methods Three male Sprague-Dawley were used, one injected with saline and two with multiple KA injections (3 x 5mg/kg) [6]. 75 days later, when spontaneous seizures started to appear, microPET (Focus 120 ) was performed under isoflurane anesthesia (2.5-3 % in air) for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) followed by MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed as SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results obtained in KA treated rats showed that [18F]UCB-H was able to detect important modifications for SV2A in relevant regions for epilepsy and appears as a valuable tool to follow in vivo SV2A through longitudinal studies. KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [less ▲]

Detailed reference viewed: 30 (1 ULg)
Full Text
See detailIN VIVO STUDY OF THE SV2A PROTEIN IN AN EPILEPTIC RAT MODEL
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017)

Introduction Epilepsy is one of the commonest neurological disorders, affecting more than 60 million people worldwide [1]. New and effective antiepileptic drugs mainly target the SV2A protein [2] but its ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders, affecting more than 60 million people worldwide [1]. New and effective antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed as a tool to study in vivo the brain expression of this isoform [3, 4]. Due to the fact that only post-mortem studies were reported so far [5] the present pilot study was undertaken in order to evaluate for the first time in vivo in rats the SV2A expression in the validated Kaïnic Acid (KA) epilepsy model [6]. Methods Three male Sprague-Dawley were used, one injected with saline (Sham) and two with multiple KA systemic injections (5mg/kg x 3) [9]. SV2A brain levels were estimated at day 75, when spontaneous seizures started to appear. Animals were anesthetized (2.5 to 3 % isoflurane), and scanned for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) in a Focus 120 microPET system and with MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed in SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results in KA treated rats presenting spontaneous seizures showed that [18F]UCB-H microPET was able to detect important reductions for the SV2A proteins in relevant regions for epilepsy [5]. Accordingly to this, we can infer that the KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [18F]UCB-H appears as a valuable tool to follow in vivo SV2A proteins through longitudinal protocols and in turn to better understand its actual role in epilepsy. References/acknowledgements This work was funded by University of Liège, F.R.S.-FNRS, Walloon Region and UCB Pharma. Alain Plenevaux is research director from F.R.S.-FNRS. [1] Alexopoulos, Epileptology, 2004 [2] Hamann et al., Eur J Pharmacol, 2008 [3] Bretin et al., Molecular Imaging and Biology, 2015 [4] Warnock et al., J Nucl Med., 2014 [5] Wang et al., J Mol Neurosci., 2014 [6] Hellier et al., Epilepsy Res., 1998 [less ▲]

Detailed reference viewed: 14 (1 ULg)
Full Text
See detail[18F]UCB-H RADIOTRACER AS A TOOL TO UNDERSTAND THE ROLE OF THE SV2A PROTEIN
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important both in normal as in pathological process (1, 2 ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important both in normal as in pathological process (1, 2). Until now, only one study in vivo has been reported, showing a reduction of SV2A levels in the epilepsy (3). [18F]UCB-H was developed like a current tool to study the role of SV2A with in vivo techniques (4, 5), and as a tool in clinical investigations. The objective of this research was to evaluate the radiotracer specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Standard Uptake Value (SUV) and Distribution Volume (VT) were calculated and the correlation between both parameters was determined. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Pearson Correlation between SUV and VT was strong, with a value of 0.955. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy. 1) Van Vliet et al., 2009. Epilepsia 2) Crèvecœur et al., 2013. BMC Neurosci. 3) Finnema et al., 2016; Sci Transl Med. 4) Bretin et al., 2013.EJNMMI Res 5) Bretin et al., 2015.Mol Imaging Biol [less ▲]

Detailed reference viewed: 15 (2 ULg)
Full Text
Peer Reviewed
See detailAltered functional brain connectivity in patients with visually induced dizziness
Van Ombergen, Angelique; Heine, Lizette ULg; Jillings, Steven et al

in NeuroImage (2017), 14

Background: Vestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visually induced dizziness (VID). These patients therefore experience ... [more ▼]

Background: Vestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visually induced dizziness (VID). These patients therefore experience dizziness, discomfort, disorientation and postural unsteadiness. The underlying pathophysiology of VID is still poorly understood. Objective: The aimof the current explorative study was to gain a first insight in the underlying neural aspects of VID. Methods:We included 10 VID patients and 10 healthymatched controls, all ofwhich underwent a resting state fMRI scan session. Changes in functional connectivitywere explored bymeans of the intrinsic connectivity contrast (ICC). Seed-based analysis was subsequently performed in visual and vestibular seeds. Results: We found a decreased functional connectivity in the right central operculum (superior temporal gyrus), as well as increased functional connectivity in the occipital pole in VID patients as compared to controls in a hypothesis-free analysis. A weaker functional connectivity between the thalamus and most of the right putamen was measured in VID patients in comparison to controls in a seed-based analysis. Furthermore, also by means of a seed-based analysis, a decreased functional connectivity between the visual associative area and the left parahippocampal gyrus was found in VID patients. Additionally,we found increased functional connectivity between thalamus and occipital and cerebellar areas in the VID patients, as well as between the associative visual cortex and both middle frontal gyrus and precuneus. Conclusions:We found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment. [less ▲]

Detailed reference viewed: 36 (2 ULg)
Full Text
Peer Reviewed
See detailRelating pessimistic memory predictions to Alzheimer’s disease brain structure
Genon, Sarah ULg; Simon, Jessica ULg; Bahri, Mohamed Ali ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2016), 85

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory ... [more ▼]

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory retrieval and investigated the neural correlates of pessimistic predictions for successfully retrieved memories in AD patients. AD patients and healthy older participants provided predictive judgements on their recognition performance before retrieval of famous (semantic) and recently learned (episodic) names. Correlations between grey matter volume (GMV) in T1 images and behavioural scores were examined with multivariate (PLS) and univariate (GLM) analyses in AD patients. AD patients showed a significant proportion of successful name recognition preceded by pessimistic prediction (Prediction_low_hits) in episodic memory. PLS revealed that behavioural pattern in AD patients was related with a mainly right lateralized pattern of GMV decrease including medial temporal lobe and posterior cingulate cortex, but also right ventrolateral prefrontal cortex (VLPFC). GLM further confirmed that pessimistic prediction negatively correlated with GMV in VLPFC. Thus, impaired monitoring processes (possibly influenced by inaccurate beliefs) allowing inferences about one’s own memory performance are primarily related to decrease GMV in VLPFC in AD patients. [less ▲]

Detailed reference viewed: 89 (14 ULg)
Full Text
See detailEVALUATING THE SPECIFICITY OF [18F]UCB-H FOR THE ISOFORM SV2A, COMPARED WITH ISOFORMS SV2B AND SV2C
Serrano Navacerrada, Maria Elisa ULg; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

Poster (2016, November 18)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the epilepsy (1, 2). [18F]UCB-H was developed like a tool to study the role of this isoform with neuroimaging techniques (3, 4). The objective of this study was to evaluate its specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Data were expressed in Standard Uptake Value and then, the area under the curve was calculated for the total process. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy. [less ▲]

Detailed reference viewed: 42 (6 ULg)
Full Text
Peer Reviewed
See detailResting-state Network-specific Breakdown of Functional Connectivity during Ketamine Alteration of Consciousness in Volunteers
BONHOMME, Vincent ULg; VANHAUDENHUYSE, Audrey ULg; Demertzi, Athina ULg et al

in Anesthesiology (2016), 125(5), 873-878

Background: Consciousness-altering anesthetic agents disturb connectivity between brain regions composing the resting-state consciousness networks (RSNs). The default mode network (DMn), executive control ... [more ▼]

Background: Consciousness-altering anesthetic agents disturb connectivity between brain regions composing the resting-state consciousness networks (RSNs). The default mode network (DMn), executive control network, salience network (SALn), auditory network, sensorimotor network (SMn), and visual network sustain mentation. Ketamine modifies consciousness differently from other agents, producing psychedelic dreaming and no apparent interaction with the environment. The authors used functional magnetic resonance imaging to explore ketamine-induced changes in RSNs connectivity. Methods: Fourteen healthy volunteers received stepwise intravenous infusions of ketamine up to loss of responsiveness. Because of agitation, data from six subjects were excluded from analysis. RSNs connectivity was compared between absence of ketamine (wake state [W1]), light ketamine sedation, and ketamine-induced unresponsiveness (deep sedation [S2]). Results: Increasing the depth of ketamine sedation from W1 to S2 altered DMn and SALn connectivity and suppressed the anticorrelated activity between DMn and other brain regions. During S2, DMn connectivity, particularly between the medial prefrontal cortex and the remaining network (effect size β [95% CI]: W1 = 0.20 [0.18 to 0.22]; S2 = 0.07 [0.04 to 0.09]), and DMn anticorrelated activity (e.g., right sensory cortex: W1 = −0.07 [−0.09 to −0.04]; S2 = 0.04 [0.01 to 0.06]) were broken down. SALn connectivity was nonuniformly suppressed (e.g., left parietal operculum: W1 = 0.08 [0.06 to 0.09]; S2 = 0.05 [0.02 to 0.07]). Executive control networks, auditory network, SMn, and visual network were minimally affected. Conclusions: Ketamine induces specific changes in connectivity within and between RSNs. Breakdown of frontoparietal DMn connectivity and DMn anticorrelation and sensory and SMn connectivity preservation are common to ketamine and propofol-induced alterations of consciousness. [less ▲]

Detailed reference viewed: 71 (17 ULg)
Full Text
Peer Reviewed
See detailEnabling efficient PET imaging of Synaptic Vesicle glycoprotein 2A (SV2A) with a robust and one-step radiosynthesis of a highly potent 18F-labelled ligand ([18F]UCB-H)
Warnier, Corentin ULg; Lemaire, Christian ULg; Becker, Guillaume ULg et al

in Journal of Medicinal Chemistry (2016), 59

We herein describe the straightforward synthesis of a stable pyridyl(4- methoxyphenyl)iodonium salt and its [18F]radiolabelling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F ... [more ▼]

We herein describe the straightforward synthesis of a stable pyridyl(4- methoxyphenyl)iodonium salt and its [18F]radiolabelling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F]UCB-H ([18F]7), a PET tracer for the imaging of Synaptic Vesicle glycoprotein 2A (SV2A). Over the course of one year, 50 automated productions provided 34±2% of injectable [18F]7 from up to 285 GBq (7.7 Ci) of [18F]fluoride in 50 minutes (uncorrected radiochemical yield. Specific Activity = 815±185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity and cGMP productions attests to its practicality and reliability for the production of large doses of [18F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field. [less ▲]

Detailed reference viewed: 57 (15 ULg)
Full Text
Peer Reviewed
See detailBiodistribution of Novel 68Ga-Radiolabelled HER2 Aptamers in Mice
Gijs, Marlies; Becker, Guillaume ULg; Plenevaux, Alain ULg et al

in Journal of Nuclear Medicine and Radiation Therapy (2016), 7(5),

Background: Two novel HER2 aptamers were recently selected with great potential for the in vitro diagnosis of HER2-positive cancer. The goal of this study was to examine the in vivo diagnostic potential ... [more ▼]

Background: Two novel HER2 aptamers were recently selected with great potential for the in vitro diagnosis of HER2-positive cancer. The goal of this study was to examine the in vivo diagnostic potential of these HER2 aptamers. Methods: Both HER2 aptamers were radiolabelled with 68Ga, injected in mice bearing a HER2-positive and HER2-negative tumour and evaluated by PET/MRI. Results: Ex vivo bio distribution analysis revealed high uptake in the blood, tissues and organs, except the brain. Interestingly, this high uptake was explained by the slow blood clearance due to non-specific aptamer binding to blood proteins. We observed accumulation of radioactivity in both tumours in time. Although higher uptake in the HER2-positive tumour compared to the HER2-negative tumour was observed, this was accompanied with more necrosis in the HER2-negative tumour, which was observed by 18FDG PET/CT. Conclusion: This work presents a first step towards the development of 68Ga-labelled aptamers for molecular cancer imaging. [less ▲]

Detailed reference viewed: 80 (14 ULg)
Full Text
Peer Reviewed
See detailEffects of aging on task- and stimulus-related cerebral attention networks
Kurth, Sophie ULg; Majerus, Steve ULg; Bastin, Christine ULg et al

in Neurobiology of Aging (2016), 44

Interactions between a dorsal attention (DAN) and a ventral attention cerebral network (VAN) have been reported in young participants during attention or short term memory (STM) tasks. Since it remains an ... [more ▼]

Interactions between a dorsal attention (DAN) and a ventral attention cerebral network (VAN) have been reported in young participants during attention or short term memory (STM) tasks. Since it remains an under-investigated question, age effects on DAN and VAN activity and their functional balance were explored during performance of a STM task. Older and young groups showed similar behavioral patterns of results. At the cerebral level, DAN activation increased as a function of increasing STM load in both groups, suggesting preserved activity in DAN during healthy aging. Age-related over-recruitment in regions of the DAN in the higher task load raised the question of compensation attempt versus less efficient use of neural resources in older adults. Lesser decrease of VAN activation with increasing load and decreased stimulus-driven activation in the VAN, especially in the higher load, in older participants suggested age-related reduced response in the VAN. However, functional connectivity measures showed that VAN was still functionally connected to the DAN in older participants. [less ▲]

Detailed reference viewed: 67 (32 ULg)