Sylvie Chalon

• DR2 Inserm
• University of Tours

Background Selection of the most promising radiotracer candidates for radiolabeling is a difficult step in the development of radiotracer pharmaceuticals, especially for the brain. Mass spectrometry (MS) is an alternative to study ex vivo the characteristics of candidates, but most MS studies are complicated by the pharmacologic doses injected and...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of AS...

Age-related neurodegenerative diseases have in common the occurrence of cognitive impairment, a highly incapacitating process that involves the cholinergic neurotransmission system. The vesicular acetylcholine transporter (VAChT) positron emission tomography (PET) tracer [¹⁸F]fluoroethoxybenzovesamicol ((−)-[¹⁸F]FEOBV) has recently demonstrated its...

Despite an apparently silent imaging, some patients with mild traumatic brain injury (TBI) experience cognitive dysfunctions, which may persist chronically. Brain changes responsible for these dysfunctions are unclear and commonly overlooked. It is thus crucial to increase our understanding of the mechanisms linking the initial event to the functio...

Preterm birth before the gestational age of 32 weeks is associated with the occurrence of specific white matter damage (WMD) that can compromise the neurological outcome. These white matter abnormalities are embedded in more global brain damage defining the encephalopathy of prematurity (EoP). A global reduction in white matter volume that correspo...

e12557 Background: Triple-negative breast cancer (TNBC) tends to exhibit aggressive behavior lacking from targeted therapies. Tumor-associated-macrophages (TAMs as M2 and M1 macrophages) are interest targets in TNBC to approach the tumor patient immunity. The mitochondrial translocator protein (TSPO), a sensitive marker for macrophages, could be in...

In a previous study, we showed that viniferin decreased amyloid deposits and reduced neuroinflammation in APPswePS1dE9 transgenic mice between 3 and 6 months of age. In the present study, wild type and APPswePS1dE9 transgenic mice were treated from 7 to 11 or from 3 to 12 months by a weekly intraperitoneal injection of either 20 mg/kg viniferin or...

Melatonin has shown promising neuroprotective effects due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties, making it a candidate drug for translation to humans in conditions that compromise the developing brain. Our study aimed to explore the impact of prenatal melatonin in an inflammatory/infectious context on GABAergic neuron...

To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson's disease. It was recently observed in a rodent model of Alzheimer's disease that the interaction between the a7 subtype of nicotinic acetylcholine receptor (a7-nAChR) and sigma-1 receptor (s1-R) could exert neuroprotective effects...

We synthesized 5‐[18F]‐Fluoro‐1H‐indol‐2‐yl)(4‐methyl‐1‐piperazinyl)methanone ([18F]5) via a Suzuki approach starting from a protected pinacol borane precursor followed by acidic hydrolysis of the t‐Boc protecting group. The non‐optimized radiochemical yield was 5.7 ± 1.35%, radiochemical purity was over 99% and molar activity was 100.7 ± 34.5 GBq/...

Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary ta...

Alzheimer's disease (AD) leads to the progressive loss of memory and other cognitive functions. It is the most common form of dementia in the elderly and has become a major public health problem due to the increase in life expectancy. Although the detection of AD is based on several neuropsychological tests, imaging and biological analyses, none of...

Altered glutamate signaling is thought to be involved in a myriad of psychiatric disorders. Positron emission tomography (PET) imaging with [18F]FPEB allows assessing dynamic changes in metabotropic glutamate receptor 5 (mGluR5) availability underlying neuropathological conditions. The influence of endogenous glutamatergic levels into receptor bind...

Longitudinal mouse PET imaging is becoming increasingly popular due to the large number of transgenic and disease models available but faces challenges. These challenges are related to the small size of the mouse brain and the limited spatial resolution of microPET scanners, along with the small blood volume making arterial blood sampling challengi...

Purpose The nicotinic acetylcholine alpha-7 receptors (α7R) are involved in a number of neuropsychiatric and neurodegenerative brain disorders such as Parkinson’s disease (PD). However, their specific pathophysiologic roles are still unclear. In this context, we studied the evolution of these receptors in vivo by positron emission tomography (PET)...

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative protei...

In this paper we describe the design and synthesis of bis(Het)Aryl-1,2,3-triazole quinuclidine α7R ligands using an efficient three-step sequence including a Suzuki-Miyaura cross coupling reaction with commercially available and home-made boron derivatives. The exploration of SAR required the preparation of uncommon boron derivatives. Forty final d...

The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim,...

Introduction: A rapid transition from a clinical-based classification to a pathology-based classification of neurodegenerative conditions, largely promoted by the increasing availability of imaging biomarkers, is emerging. The Framework for Innovative Multi-tracer molecular Brain Imaging, funded by the EU Joint Program - Neurodegenerative Disease...

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Interestingly, it has already been shown that an intracerebral administration of neuropeptide Y (NPY) decreases the neurodegeneration induced by 6‐hydroxydopamine (6‐OHDA) in rodents and prevents loss of dopamine (DA) and DA transport...

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disea...

A series of novel derivatives exhibiting high affinity and selectivity towards the COX-2 enzyme in the (aza) indazole series was developed. A short synthetic route involving a bromination/arylation sequence under microwave irradiation and direct C–H activation were established in the indazole and azaindazole series respectively. In vitro assays wer...

The P2X7 receptor plays a significant role in microglial activation, and as a potential drug target, the P2X7 receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X7 receptor, to which end four adamantanyl benzamide analogues with high af...

Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR) activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying m...

Parkinson's disease (PD) is characterized by the degeneration of the dopamine-producing cells in the substantia nigra. Early diagnosis and therapy is essential at the molecular level before initiation of symptomatic changes. Blood-brain barrier (BBB) penetration still remains a major challenge. Increased brain penetration and targeting can be achie...

Background: IMAkinib® program is an innovative approach, based on Nanocyclix® chemistry technology, which aims to develop new Tyrosine Kinase Inhibitors (TKIs) radiotracers used for Positron Emission Tomography (PET). The epidermal growth factor receptor (EGFR) is an established target for the treatment of advanced non-small cell lung cancer (NSCLC...

The chronic and relapsing nature of addiction suggests that drugs produce persistent adaptations in the brain that make individuals with drug addiction particularly sensitive to drug-related cues and stress and incapable of controlling drug-seeking and drug-taking behavior. In animal models, several long-lasting neuroadaptations have been described...

Maternal infection/inflammation represents one of the most important factors involved in the etiology of brain injury in newborns. We investigated the modulating effect of prenatal melatonin on the neonatal brain inflammation process resulting from maternal intraperitoneal (i.p.) lipopolysaccharide (LPS) injections. LPS (300 μg/kg) was administered...

Subarachnoid hemorrhage (SAH) can lead to delayed cerebral ischemia, which increases the rate of morbidity and mortality. The detection of microglial activation may serve as a biomarker for the identification of patients at risk of this deleterious consequence. We assessed this hypothesis in a rat model of SAH in which the exploration of neuroinfla...

Recent mouse studies of the presymptomatic stage of Alzheimer’s disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNF α contributes to increased A β production from the A β precursor protein (APP), we assessed a putativ...

Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use o...

1 Department of Radiopharmacy, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey. 2 UMR INSERM U930, Faculty of Medicine, Université François Rabelais de Tours, Tours, France.

Positron emission tomography (PET) molecular imaging of brain targets is a powerful tool to diagnose, follow up, and develop treatments and personalized medicine for a number of acute and chronic brain disorders. The availability of β+ emitter tracers labelled with [(11)C] or [(18)F] having optimal characteristics of affinity and selectivity for al...

The inverse association between nicotine intake and Parkinson's disease (PD) is well established and suggests that this molecule could be neuroprotective through anti-inflammatory action mediated by nicotinic receptors, including the α7-subtype (α7R). The objective of this study was to evaluate the effects of an agonist of α7R, PHA 543613, on stria...

Segmentation of dynamic PET images is needed to extract the time activity curves (TAC) of regions of interest (ROI). These TAC can be used in compartmental models for in vivo quantification of the radiotracer target. While unsupervised clustering methods have been proposed to segment PET sequences, they are often sensitive to initial conditions or...

S-substituted thiotriazoles are formed from triazolothiadiazoles and arylcuprates, Grignard-reagents and organolithium compounds.

Methylphenidate (MPH) is a commonly used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adult with ADHD and narcoleptic patients raises the question of how the brain would be impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term...

In this paper, we extend the gradient vector flow field to the vector-valued case for robust variational segmentation of 4D images with active surfaces. Instead of only exploiting scalar edge strength in order to identify vector edges, we propagate both directions and amplitudes of vector gradients computed from the analysis of a structure tensor o...

In this paper, we extend the gradient vector flow field for robust variational segmentation of vector-valued images. Rather than using scalar edge information, we define a vectorial edge map derived from a weighted local structure tensor of the image that enables the diffusion of the gradient vectors in accurate directions through the 4DGVF equatio...

In this paper, we generalize the gradient vector flow field to vector-valued images. We base our method on the definition of a structure tensor that is calculated according to a blind estimation of contrast in the different channels and that exploits the whole spatio-spectral information, hence reducing sensitivity to noise and better defining orie...

Keywords: Synthetic methods / Domino reactions / Sulfur heterocycles / Nitrogen heterocycles / Grignard reagents An efficient and convenient method was developed for the formation of S-substituted thiotriazoles through an unprece-dented organometallic addition and subsequent ring-open-ing sequence of 3-substituted [1,2,4]triazolo[3,4-b][1,3,4]thia-...

Excitotoxicity leads to an inflammatory reaction involving an overexpression of: translocator protein 18 kDa (TSPO) in cerebral microglia and astrocytes. Therefore, we performed ex vivo explorations with [125]-CLINDE, a TSPO-specific radioligand, to follow the time course of TSPO expression, in parallel with lesion progression, over 90 days after i...

We studied concomitantly the level of neuroinflammation and Aβ load in the APPswePS1dE9 transgenic mouse model of Alzheimer’s disease using PET imaging. The TSPO tracer [18F]DPA-714 was used to measure neuroinflammation and [18F]AV-45 for Aβ load in mice at 6, 9, 12, 15 and 19 months of age. At 19 months, we also analysed the neuroinflammatory and...

We examined whether [(18)F]LBT-999 ((E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4'-tolyl)nortropane) is an efficient positron emission tomography (PET) tracer for the quantification of the dopamine transporter (DAT) in the healthy rat brain. PET studies were performed using several experimental designs, i.e. test-retest, co-injection with differe...

Background/aims: Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Its relationship with underlying β amyloid deposition remains unclear. In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands when used with positron emission tomography (PET). The t...

Segmentation is often required for the analysis of dynamic positron emission tomography (PET) images. However, noise and low spatial resolution make it a difficult task and several supervised and unsupervised methods have been proposed in the literature to perform the segmentation based on semi-automatic clustering of the time activity curves of vo...

The quantification of dynamic PET images requires the definition of regions of interest. The manual delineation is a time consuming and unreproducible process due to the poor resolution of PET images. Approaches were proposed in the literature to classify the kinetic profiles of voxels, however, they are generally either sensitive to initial condit...

Mother–young relationships in sheep are characterized by individual recognition and a rapidly developing exclusive bond. The authors examined the role of opioids in establishment of the lamb's preference for its mother. Newborn lambs received the opioid receptor antagonist naltrexone (0.0, 1.5, or 3.0 mg/kg ip), and lambs were tested at 24 hr and 4...

Epidemiological and experimental data implicate maternal infection and inflammation in the etiology of brain white matter injury, which may lead to cerebral palsy in preterm newborns. Our aim was to investigate motor development of the offspring after maternal administration of lipopolysaccharide (LPS). Wistar rats were intraperitoneally injected w...

Epidemiological and experimental data implicate maternal infection and inflammation in the aetiology of brain white matter injury which may lead to cerebral palsy in preterm newborns. Our aim was to investigate motor development of the offspring after maternal administration of LPS. Wistar rats were intraperitoneally injected with E.Coli LPS or sal...

Heme oxygenase-1 (HO-1) induction is associated with beneficial or deleterious effects depending on the experimental conditions adopted and the neurodegenerative rodent models used. The present study aimed first to evaluate the effects of cerebral HO-1 induction in an in vivo rat model of neuroinflammation by intrastriatal injection of quinolinic a...

The blood-brain barrier plays a major role in controlling the delivery of therapeutic and imaging agents to the brain. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First...

As neuroinflammatory processes are involved in the pathogenesis of Parkinson's disease (PD), we achieved the longitudinal evaluation of them in parallel with the modifications of dopaminergic function at several time-points after 6-hydroxydopamine (6-OHDA) lesion in the rat mimicking an early stage of PD. After unilateral intrastriatal 6-OHDA admin...

There is evidence that excitotoxicity and prolonged microglial activation are involved in neuronal death in neurodegenerative disorders. Activated microglia express various molecules, including the translocator protein 18 kDa (TSPO; formerly known as the peripheral benzodiazepine receptor) on the outer mitochondrial membrane. The TSPO is a novel ta...

The double-stranded RNA-dependent protein kinase (PKR) is switched on by a wide range of stimuli, including the amyloid peptide. Then, PKR transmits signals to the translational machinery, apoptosis and inflammatory signaling pathways by interacting with some adapters. In virus-infected cells, PKR engages the nucleus factor κB (NF-κB) pathway. In m...

Positron emission tomography (PET) images are corrupted by noise. This is especially true in dynamic PET imaging where short frames are required to capture the peak of activity concentration after the radiotracer injection. High noise results in a possible bias in quantification, as the compartmental models used to estimate the kinetic parameters a...

Unipolar depression is the leading causes of disease burden in high income countries (1). Conventional antidepressant treatment fails to treat majority of the patients. Finding of co-prevalence of major depressive disorder with inflammatory diseases (2) has further complicated the picture. Episodes of depression have been characterized by an increa...

The blood-brain barrier plays a major role in controlling the delivery of therapeutic and imaging agents to the brain. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First...

Cocaine-induced sensitization induces long-term neuroplastic changes in the striatum. Among these, extracellular signal-regulated kinase (ERK) is a fundamental component in striatal gene and epigenetic regulation and plays an important role in reward processes. As previous studies suggested that the chemokine CCL2 enhanced striatal dopamine release...

The gibbon ape leukemia virus (GALV), the amphotropic murine leukemia virus (AMLV) and the human T-cell leukemia virus (HTLV) are retroviruses that specifically bind nutrient transporters with their envelope glycoproteins (Env) when entering host cells. Here, we used tagged ligands derived from GALV, AMLV, and HTLV Env to monitor the distribution o...

Neuroinflammation is involved in stroke pathophysiology and might be imaged using radioligands targeting the 18 kDa translocator protein (TSPO). We studied microglial reaction in brain areas remote from the primary lesion site in two rodent models of focal cerebral ischaemia (permanent or transient) using [125I]-CLINDE, a promising TSPO single phot...

Environmental challenges during the prenatal period can result in behavioral abnormalities and cognitive deficits that appear later in life such as autism. Prenatal exposure to valproic acid, ethanol, thalidomide and misoprostol has been shown to be associated with an increased incidence of autism. In addition, rodents exposed in utero to some of t...

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A characteristic of prion diseases which affect both animals and humans is the aggregation of PrP amyloid fibrils in the brain, associated with a chronic inflammatory response dominated by microglial activation. In this study, we hypothesised that specific ligands of the 18-kDa translocator protein (TSPO) would be effective in the evaluation of mic...

3,4-methylenedioxymethamphetamine or MDMA (ecstasy) is a synthetic illicit drug which is widely consumed throughout the world. Drug abuse during pregnancy may have an impairing effect on the progeny of drug-abusing mothers. The purpose of the present study was to assess the effect of prenatal MDMA exposure on the progeny development, using a rat mo...

In order to explore whether some aspects of the autistic phenotype could be related to impairment of the serotonergic system, we chose an animal model which mimics a potential cause of autism, i.e. rats exposed to valproate (VPA) on the 9th embryonic day (E9). Previous studies have suggested that VPA exposure in rats at E9 caused a dramatic shift i...

Introduction Des études soulignent la composante inflammatoire dans la physiopathologie de la maladie d’Alzheimer (MA). Le spectre des médiateurs inflammatoires dont TNFα, IL-1β et IL-6 implique de nombreuses voies de signalisation, conduisant à la mort neuronale. Il est bien connu que la MA se caractérise aussi par une activation de la voie PKR (d...

The �? autoradiography is commonly used in preclinical research. This technique is able to locate, in 2 dimensions with a high spatial resolution, molecule labeled with �? emitters. We report on the development of an integrated and transportable device base on the PIM (Parallel Ionization Multiplier) structure able to perform the image of 10 micros...

Several arguments have been proposed to support the hypothesis that supplementation with essential fatty acids (EFAs) could be valuable in the treatment of attention deficit-hyperactivity disorder (ADHD). Indeed, this disorder seems to involve the monoaminergic systems which have been shown to be affected by polyunsaturated fatty acid (PUFA) status...

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model provides a valuable paradigm of the energy deficiency disorders found in childhood. In such disorders, anticonvulsants may provide neuroprotection by modulating cellular energy consumption and by exerting favorable pleiotropic effects on neuronal survival. To verify such hypothesis...

The basal ganglia, which are interconnected in the striato-nigral dopaminergic network, are affected in several childhood diseases including Leigh syndrome (LS). LS is the most common mitochondrial disorder affecting children and usually arise from inhibition of the respiratory chain. This vulnerability is attributed to a particular susceptibility...

Single photon emission tomography (SPECT) and positron emission tomography (PET) are techniques to study in vivo neurotransmitter systems, neuroinflammation and amyloid deposits in normal human brain and in dementia. These methods used to explore the integrity of dopaminergic, cholinergic and serotonergic systems in Alzheimer's disease and in other...

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BACKGROUND: The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroin...