Radiopharmaceuticals for PET imaging of neuroinflammation - Les radiopharmaceutiques pour l’imagerie TEP de la neuroinflammation

Abstract Recently, accumulating evidence has revealed that neuroinflammation appears to be the cornerstone of many neurological diseases including stroke, multiple sclerosis, Alzheimer's disease or Parkinson's disease. Neuroinflammation causes neuronal damages by activation of numerous cells and molecular mediators in diseases involving the inflammatory process. In this article, we focus on noninvasive molecular imaging of radioligands that target inflammatory cells and molecules involved in neuroinflammation. PET is in fact one of the most promising imaging techniques to visualize and quantify neuroinflammation in vivo. We have also summarized the potential neuroinflammation imaging targets and corresponding PET radioligands. Résumé Des données scientifiques récentes et de plus en plus nombreuses ont mis en évidence le rôle central joué par le processus de neuroinflammation dans la physiopathologie de nombreuses maladies neurologiques, telles que l’accident vasculaire cérébral, la sclérose en plaques, la maladie d’Alzheimer ou encore la maladie de Parkinson. Dans ces maladies impliquant le processus inflammatoire, la neuro-inflammation cause en effet des dommages neuronaux par activation de nombreuses cellules et médiateurs moléculaires. L’imagerie par tomographie par émission de positons (TEP) apparaît comme une approche prometteuse pour visualiser et quantifier in vivo la neuro-inflammation de façon non invasive, grâce en particulier au développement de radioligands ciblant spécifiquement diverses molécules impliquées dans cette réaction inflammatoire cérébrale. Dans cette revue sont présentés les cibles moléculaires potentielles pour l’imagerie TEP de la neuro-inflammation ainsi que les médicaments radiopharmaceutiques correspondants

Innovative Molecular Imaging for Clinical Research, Therapeutic Stratification, and Nosography in Neuroscience.

Over the past few decades, several radiotracers have been developed for neuroimaging applications, especially in PET. Because of their low steric hindrance, PET radionuclides can be used to label molecules that are small enough to cross the blood brain barrier, without modifying their biological properties. As the use of 11C is limited by its short physical half-life (20 min), there has been an increasing focus on developing tracers labeled with 18F for clinical use. The first such tracers allowed cerebral blood flow and glucose metabolism to be measured, and the development of molecular imaging has since enabled to focus more closely on specific targets such as receptors, neurotransmitter transporters, and other proteins. Hence, PET and SPECT biomarkers have become indispensable for innovative clinical research. Currently, the treatment options for a number of pathologies, notably neurodegenerative diseases, remain only supportive and symptomatic. Treatments that slow down or reverse disease progression are therefore the subject of numerous studies, in which molecular imaging is proving to be a powerful tool. PET and SPECT biomarkers already make it possible to diagnose several neurological diseases in vivo and at preclinical stages, yielding topographic, and quantitative data about the target. As a result, they can be used for assessing patients' eligibility for new treatments, or for treatment follow-up. The aim of the present review was to map major innovative radiotracers used in neuroscience, and explain their contribution to clinical research. We categorized them according to their target: dopaminergic, cholinergic or serotoninergic systems, β-amyloid plaques, tau protein, neuroinflammation, glutamate or GABA receptors, or α-synuclein. Most neurological disorders, and indeed mental disorders, involve the dysfunction of one or more of these targets. Combinations of molecular imaging biomarkers can afford us a better understanding of the mechanisms underlying disease development over time, and contribute to early detection/screening, diagnosis, therapy delivery/monitoring, and treatment follow-up in both research and clinical settings

CIRCULAR ROAD SIGN EXTRACTION FROM STREET LEVEL IMAGES USING COLOUR, SHAPE AND TEXTURE DATABASE MAPS

Detection and recognition of road signs can constitute useful tools in driving assistance and autonomous navigation systems. We aim at generating a road sign database that can be used for both georeferencing in autonomous vehicle navigation systems and also in high scale 3D city modelling. This paper proposes a robust algorithm that can detect road signs shape and recognizes their types.

Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One 7:e52941 Cortes C, Vapnik V

Abstract There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18 F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney's test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18 F-DPA-714 was increased in ALS patients during the ''time of diagnosis'' phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation

Stability of Antibiotics in Portable Pumps Used for Bronchial Superinfection: Guidelines for Prescribers

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Detection and quantification of remote microglial activation in rodent models of focal ischaemia using the TSPO radioligand CLINDE.

Purpose: Neuroinflammation is involved in stroke pathophysiology and might be imaged using radioligands targeting the 18 kDa translocator protein (TSPO). Methods: 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 photon emission computed tomography radioligand. Results: In a mouse model of permanent middle cerebral artery occlusion (MCAO), ex vivo autoradiographic studies demonstrated, besides in the ischaemic territory, accumulation of [125I]-CLINDE in the ipsilateral thalamus with a binding that progressed up to 3 weeks after MCAO. [125I]- CLINDE binding markedly decreased in animals preinjected with either unlabelled CLINDE or PK11195, while no change was observed with flumazenil pre-treatment, demonstrating TSPO specificity. In rats subjected to transient MCAO, [125I]-CLINDE binding in the ipsilateral thalamus and substantia nigra pars reticulata (SNr) was significantly higher than that in contralateral tissue. Moreover, [125I]-CLINDE binding in the thalamus and SNr was quantitatively correlated to the ischaemic volume assessed by MRI in the cortex and striatum, respectively. Conclusion: Clinical consequences of secondary neuronal degeneration in stroke might be better treated thanks to the discrimination of neuronal processes using in vivo molecular imaging and potent TSPO radioligands like CLINDE to guide therapeutic interventions. © 2010, Springer