Research Steven Staelens

Abstract

During the past decades, many traditional medical imaging techniques have been established for routine use. These imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and radionuclide imaging (PET/SPECT) are widely applicable for both small animal and clinical imaging, diagnosis and treatment. A unique feature of molecular imaging is the use of molecular imaging agents (either endogenous molecules or exogenous tracers) to image particular targets or pathways and to visualize, characterize, and quantify biological processes in vivo. Dedicated high-resolution small animal imaging systems such as microPET/CT scanners have emerged as important new tools for preclinical research. Considerable benefits include the robust and non-invasive nature of these small animal imaging experiments, enabling longitudinal studies with the animal acting as its own control and reducing the number of laboratory animals needed. This approach of "miniaturised" clinical scanners efficiently closes the translational feedback loop to the hospital, ultimately resulting in improved patient care and treatment. By this underlying submission, our consortium aims to renew our 2011 microPET/CT scanners after their ten-year lifetime by a digital up-to-date system in order to continue our preclinical molecular imaging studies in several research fields, including neuroscience, oncology and tracer development.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Augustyns Koen
• Co-promoter: Bertoglio Daniele
• Co-promoter: Elvas Filipe
• Co-promoter: Stroobants Sigrid
• Co-promoter: Van Der Veken Pieter
• Co-promoter: Verhaeghe Jeroen

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

The envisaged core facility brings together key preclinical imaging expertise and facilities within UA located in the Uc building on CDE. This joint venture provides preclinical imaging instruments of the highest performance of all Belgian universities. Concretely, the preclinical imaging infrastructure consists of 4 high‐field MRI systems with dedicated RF coils, 2 microPET/CT systems, 1 microSPECT/PET/CT. Using this equipment, virtual sections can be made through a living laboratory animal (which may or may not be a model for a particular pathology) enabling to quantitatively monitor various anatomical, morphological, physiological and molecular processes over time in the same animal. These techniques play a crucial role in basic and applied biomedical and pharmaceutical research and because the same techniques are used in humans/patients (translationally) they are vital for clinical diagnostics and research into early biomarkers of diseases and therapy follow‐up. In addition to the in‐vivo multi‐modal imaging systems, access to Bioluminescence/Fluorescence camera, animal monitoring (pulse oxygenation, temperature, respiration, ECG and EEG), microsurgery, and a radioprotected laboratory animal animalarium (150 laboratory animals single housed) are available.

Researcher(s)

• Promoter: Verhoye Marleen
• Co-promoter: Bertoglio Daniele
• Co-promoter: Elvas Filipe
• Co-promoter: Staelens Steven
• Co-promoter: Verhaeghe Jeroen

Research team(s)

• Bio-Imaging lab

Project type(s)

• Research Project

Abstract

IMARK capitalizes on the deeply rooted expertise in biomedical imaging at the University of Antwerp to push the boundaries of precision medicine. By resolving molecular and structural patterns in space and time, IMARK aims at expediting biomarker discovery and development. To this end, it unites research groups with complementary knowledge and tools that cover all aspects of imaging-centred fundamental research, preclinical validation and clinical evaluation. IMARK harbours high-end infrastructure for electron and light microscopy, mass spectrometry imaging, magnetic resonance imaging, computed tomography, positron emission tomography and single-photon emission computed tomography. Moreover, IMARK members actively develop correlative approaches that involve multiple imaging modalities to enrich information content, and conceive dedicated image analysis pipelines to obtain robust, quantitative readouts. This unique blend of technologies places IMARK in an excellent position as preferential partner for public-private collaborations and offers strategic advantage for expanding the flourishing IP portfolio. The major application fields of the consortium are neuroscience and oncology. With partners from the Antwerp University Hospital and University Psychiatric Centre Duffel, there is direct access to patient data/samples and potential for translational studies.

Researcher(s)

• Promoter: De Vos Winnok
• Co-promoter: Baets Jonathan
• Co-promoter: Baggerman Geert
• Co-promoter: Bertoglio Daniele
• Co-promoter: Bogers John-Paul
• Co-promoter: Coppens Violette
• Co-promoter: Elvas Filipe
• Co-promoter: Keliris Georgios A.
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Mertens Inge
• Co-promoter: Morrens Manuel
• Co-promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Timmerman Vincent
• Co-promoter: Timmermans Jean-Pierre
• Co-promoter: Verhaeghe Jeroen
• Co-promoter: Verhoye Marleen
• Fellow: Lanens Dirk
• Fellow: Prasad Aparna

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

Neuropathological research is an interdisciplinary field, in which imaging and image-guided interventions have become indispensable. However, the rapid proliferation of ever-more inquisitive technologies and the different scales at which they operate have created a bottleneck at the level of integration, a) of the diverse image data sets, and b) of multimodal image information with omics-based and clinical repositories. To meet a growing demand for holistic interpretation of multi-scale (molecule, cell, organ(oid), organism) and multi-layered (imaging, omics, chemo-physical) information on (dys)function of the central and peripheral nervous system, we have conceived μNEURO, a consortium comprising eight established teams with complementary expertise in neurology, biomedical and microscopic imaging, electrophysiology, functional genomics and advanced data analysis. The goal of μNEURO is to expedite neuropathological research and identify pathogenic mechanisms in neurodevelopmental and -degenerative disorders (e.g., Alzheimer's Disease, epilepsy, Charcot-Marie-Tooth disease) on a cell-to-organism wide scale. Processing large spatiotemporally resolved image data sets and cross-correlating multimodal images with targeted perturbations takes center stage. Furthermore, inclusion of (pre)clinical teams will accelerate translation to a clinical setting and allow scrutinizing clinical cases with animal and cellular models. As knowledge-hub for neuro-oriented image-omics, μNEURO will foster advances for the University and community including i) novel insights in molecular pathways of nervous system disorders; ii) novel tools and models that facilitate comprehensive experimentation and integrative analysis; iii) improved translational pipeline for discovery and validation of novel biomarkers and therapeutic compounds; iv) improved visibility, collaboration and international weight fueling competitive advantage for large multi-partner research projects.

Researcher(s)

• Promoter: Sijbers Jan
• Co-promoter: Baets Jonathan
• Co-promoter: Cras Patrick
• Co-promoter: De Vos Winnok
• Co-promoter: Giugliano Michele
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Timmerman Vincent
• Co-promoter: Timmermans Jean-Pierre
• Co-promoter: Verhoye Marleen
• Co-promoter: Weckhuysen Sarah

Research team(s)

• Vision lab

Project type(s)

• Research Project

Abstract

Huntington's disease (HD) is a dominantly inherited disorder characterized by a progressive neurodegeneration of the striatum that also involves other regions, primarily the cerebral cortex. Patients display progressive motor, cognitive, and psychiatric impairment. Symptoms usually start at midlife. The mutation responsible for this fatal disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding huntingtin. The pathogenic mechanisms by which mutant huntingtin cause neuronal dysfunction and cell death remain uncertain (Menalled, 2005). The mechanism underlying HD-related suppression of inhibition has been shown to include tonic activity of metabotropic glutamate receptor subtype 5 (mGluR5) as a pathophysiological hallmark (Dvorzhak, Semtner, Faber, & Grantyn, 2013) and inhibition of glutamate neurotransmission via specific interaction with mGluRs might be interesting for both inhibition of disease progression as well as early symptomatic treatment (Scheifer et al., 2004). With the objective to elucidate the role of glutamatergic pathways using small animal PET imaging, this study aims to use several PET imaging agents as tracers in a knock-in model of Huntington's disease.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Bertoglio Daniele
• Co-promoter: Van Der Linden Annemie
• Co-promoter: Verhaeghe Jeroen
• Co-promoter: Verhoye Marleen

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Huntington's Disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by a genetic mutation in the huntingtin gene (HTT), which encodes for mutant huntingtin (mHTT), the causative agent of the disorder. Since lowering the levels of toxic mHTT is postulated to halt disease progression, the use of engineered zinc finger protein transcription repressors (ZFP-TR) to selectively suppress the mutant HTT allele represents a novel candidate treatment for HD. A major limitation in the assessment of therapeutic efficacy is the lack of objective non-invasive markers. We recently validated the first-ever radioligand to image in vivo mHTT levels using positron emission tomography (PET) imaging in mice. The aim of this project is to assess the preclinical relevance of the use of ZFP-TR at different disease stages as candidate therapeutic intervention. This work will provide proof of efficacy for an mHTT lowering HD therapy in the living (rodent) brain by measuring mHTT in parallel to molecular targets for phenotypic recovery in wellcharacterized mouse models of HD. This multi-modal approach consisting of non-invasive in vivo PET imaging in combination with magnetic resonance imaging (MRI) and post-mortem techniques will represent a strategic multi-disciplinary platform to assess the efficacy of the ZFP-TR therapeutic efficacy providing a key contribution on the timing of intervention, ultimately leading to clinical translation in the future. GENERAL -

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Verhaeghe Jeroen
• Fellow: Bertoglio Daniele

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Upgrade of the hardware of existing equipment (9.4T MRI system from Bruker) to perform state of the art MRI investigations in the brain of small animals such as mice, rats and birds. This hardware upgrade will enable implementation of all new Bruker software packages.

Researcher(s)

• Promoter: Van Der Linden Annemie
• Co-promoter: Keliris Georgios A.
• Co-promoter: Ponsaerts Peter
• Co-promoter: Sijbers Jan
• Co-promoter: Staelens Steven
• Co-promoter: Verhoye Marleen

Research team(s)

• Bio-Imaging lab

Project type(s)

• Research Project

Abstract

Epilepsy is a devastating disorder affecting 65 million people worldwide characterized by recurrent seizures. This research project will investigate a novel hypothesis connecting translocator protein (TSPO) overexpression, a hallmark of brain inflammation, and spontaneous seizure outcome during the development of epilepsy (epileptogenesis). Our hypothesis is supported by the observation that i) TSPO is highly up-regulated in epilepsy and ii) our preliminary data suggest a relationship between TSPO overexpression and spontaneous seizure outcome. Unraveling this relationship will enable us to assess TSPO as a biomarker for maladaptive neuroplasticity during epileptogenesis. Firstly, by means of translational techniques, we will investigate longitudinally the pattern of TSPO expression during epileptogenesis in vivo in the kainic acid-induced status epilepticus (KASE) model. Secondly, the role of TSPO in epileptogenesis will be investigated by the study of the effects of the absence of TSPO in the TSPO knockout mouse, and by pharmacological stimulation of TSPO in the KASE model. This innovative project will increase our understanding of brain excitability during epileptogenesis offering a biomarker to identify patients at risk and moving the field forward giving a contribution to the development of therapies to prevent acquired epilepsy.

Researcher(s)

• Promoter: Verhaeghe Jeroen
• Co-promoter: Staelens Steven
• Fellow: Bertoglio Daniele

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Huntington's disease (HD) is a dominantly inherited disorder characterized by a progressive neurodegeneration of the striatum that also involves other regions, primarily the cerebral cortex. Patients display progressive motor, cognitive, and psychiatric impairment. Symptoms usually start at midlife. The mutation responsible for this fatal disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding huntingtin. The pathogenic mechanisms by which mutant huntingtin cause neuronal dysfunction and cell death remain uncertain (Menalled, 2005). It has been established in a HD mouse model that inhibition of PDE10 improves cognition and thus PDE10 might be a good therapeutic target (Giralt et al., 2013). A pilot study of [18F]-MNI-659 PET already showed a markedly reduced binding in HD compared to healthy volunteers (Jennings et al., 2013). Furthermore, the mechanism underlying HD-related suppression of inhibition has been shown to include tonic activity of metabotropic glutamate receptor subtype 5 (mGluR5) as a pathophysiological hallmark (Dvorzhak, Semtner, Faber, & Grantyn, 2013) and inhibition of glutamate neurotransmission via specific interaction with mGluRs might be interesting for both inhibition of disease progression as well as early symptomatic treatment (Scheifer et al., 2004). With the objective to elucidate the role of phosphodiesterase and glutamatergic pathways using small animal PET imaging, this study aims to use [18F]-MNI-659 (2-(2-(3-(4-(2-[18F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazo-lin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione), a PET radiotracer with high affinity for PDE 10 and [11C]-ABP-688 (3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-(11)C-methyl-oxime), a noncompetitive and highly selective mGluR5 antagonist, as tracers in a knock-in model of Huntington's disease.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid

Research team(s)

Project type(s)

• Research Project

Abstract

We propose a novel hypothesis for the development of PTE with a central role for ECM modulating components MMP-9 and uPA. TBI results in blood-brain barrier disruption, hyperexcitability and primary damage triggering repair mechanisms such as modulation of the ECM by proteases MMP-9 and uPA. These alterations in ECM proteases MMP-9 and uPA, followed by brain inflammation, induce abnormal synaptic remodeling and epileptogenesis, ultimately leading to PTE.

Researcher(s)

• Promoter: Dedeurwaerdere Stefanie
• Promoter: Verhoye Marleen
• Co-promoter: Dedeurwaerdere Stefanie
• Co-promoter: Staelens Steven
• Fellow: Missault Stephan

Research team(s)

• Translational Neurosciences (TNW)
• Bio-Imaging lab

Project type(s)

• Research Project

Abstract

Molecular imaging of small laboratory animals typically involves a restraining procedure to avoid movement during the imaging scan. To reduce the impact of stress, animals are anesthetized, but the latter largely influences brain physiology. The current project aims to develop a prototype for awake unrestrained small animal brain positron emission tomography (PET) imaging to better mimic the clinicalsituation where human patients are seldom sedated.

Researcher(s)

• Promoter: Verhaeghe Jeroen
• Co-promoter: Staelens Steven

Research team(s)

Project type(s)

• Research Project

Abstract

Patients suffering from obsessive-compulsive disorder (OCD) present symptoms as intrusive, unwanted and recurrent thought or images (obsessions) and or repetitive behaviors (compulsions).These symptoms and behaviors become excessive and disturb significantly daily activities and lead to a low quality of life and a high burden for the family of the patient. The use of serotonin reuptake inhibitor is the most efficient strategy of treatment for OCD but 40 to 60% are refractory to this kind of drugs. So there is a need to look for new therapeutic strategies. Phosphodiesterase (PDE) 7 and 10A inhibitors has been recently proposed as potential treatment in OCD. However none study has been perform to prove this hypothesis. In vivo imaging using Positron Emission Tomography (PET) is a powerful tool to monitor the stages of disease, to study human biology, to investigate in vivo the properties of new drugs in clinical trials. This technique is quantitative and very sensitive and it is a non invasive technique which is a major advantage in brain imaging. Radiotracers are investigated to image in vivo biological targets like a receptor, an enzyme or a tumor. The aim of this project is to use PET imaging to determine the role of PDE7 and PDE10A in OCD and also verify if PDE7 and PDE10A inhibitors could be used as treatment.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Augustyns Koen
• Co-promoter: Staelens Steven
• Fellow: Thomae David

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Staelens Steven

Research team(s)

Project type(s)

• Research Project

Abstract

EGAMI stands for Expert Group Antwerp Molecular Imaging. Moreover, EGAMI is the mirror word of 'image'. EGAMI clusters the internationally recognized expertise in the profession of fundamental and biomedical imaging at the University of Antwerp: the Bio-Imaging Lab, the Molecular Imaging Center Antwerp (MICA), Radiology, the Laboratory for Cell Biology and Histology, and the Vision Lab (for post-processing of medical images). EGAMI's mission is providing an integrated research platform that comprises all aspects of multimodality translational medical imaging. Multimodality refers to the integration of information from the various imaging techniques. Within EGAMI, there is pre-clinical and clinical expertise and infrastructure for magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). EGAMI executes projects ranging from applied biomedical (imaging) and fundamental research to imaging methodologies. Die applied biomedical research focusses on the research fields neuro(bio)logy (i.e. development and validation of biomarkers (as well as therapy evaluation) for diseases like Alzheimer's, schizophrenia, multiple sclerosis etc.) and oncology (i.e. biomarkers for improved patient stratification and therapy monitoring). Since the pre-clinical biomedical research within EGAMI makes use of miniaturized versions of imaging equipment for humans (scanners) is it inherently translational, in other words initial findings acquired in animal experiments can be translated into clinical applications for improved diagnosis and treatment of patients ('from bench to bedside'). Beside the application of imaging in the biomedical research, EGAMI also conducts projects that aim to achieve an improvement and optimization of the imaging methodology. The expertise of the MICA (e.g. the development of new radiotracers) and of the Vision Lab (e.g. the development of image reconstruction, segmentation, and analysis algorithms) offers here the strategic platform to assemble intellectual property rights.

Researcher(s)

• Promoter: Van Der Linden Annemie
• Co-promoter: Parizel Paul
• Co-promoter: Sijbers Jan
• Co-promoter: Staelens Steven
• Co-promoter: Timmermans Jean-Pierre
• Fellow: Guns Pieter-Jan
• Fellow: Lanens Dirk
• Fellow: Van Putte Wouter

Research team(s)

• Bio-Imaging lab

Project type(s)

• Research Project

Abstract

In this project multimodal and multiprobe imaging techniques are applied in an animal model for obsessive-compulsive disorder (OCD) in order to investigate its neuropathophysiology without the confounding factors of human OCD research such as comorbidities and previous treatment exposure. This will allow us to identify underlying networks and the role of different neurotransmitters by in-vivo dynamic visualization of the entire brain thereby improving our fundamental understanding of the disease. Furthermore, the combination of molecular imaging with application of neurostimulation techniques such as repetitive Transcranial Magnetic Stimulation (rTMS) and Deep Brain Stimulation (DBS) in the animal model for OCD will allow optimization and evaluation of these techniques as possible treatment alternatives in later extrapolation to the clinical field.

Researcher(s)

• Promoter: Staelens Steven

Research team(s)

Project type(s)

• Research Project

Abstract

In vivo molecular imaging is a highly sensitive tool to study in vivo neuroreceptor kinetics and to visualize entire brain network dynamics in human patients as well as in small laboratory animals. Obsessive-compulsive disorder (OCD) is a chronic disabling psychiatric disease, characterized by unwanted obsessions and compulsions to temporarily neutralize the anxiety provoked by these obsessions. The prevalence of OCD is reported to be 0.8% to 3.2% and an estimated 60% of patients remain unresponsive to medical intervention. OCD is an extremely complex psychiatric disorder resulting from a pathological interplay of serotonergic (5-HT), dopaminergic (DA) and glutamatergic neurochemical dysfunctions. In this project we have three clear objectives: 1. elucidate the pathophysiology in an animal model for OCD; 2. modulate glutamate levels for better target selection; 3. evaluate novel neuromodulation techniques miniaturized for small animals. To achieve our goals we have defined three work packages with two intermediate milestones to consolidate progress or to fall back to an alternative approach. Our first work package sets up the "compulsive checking" animal model and employs Positron Emission Tomography (PET) to visualize changes in whole brain activity (FDG μPET), serotonin (MDL μPET), dopamine (Raclo μPET) as well as glutamate transmission (by Magnetic Resonance Spectroscopy) and correlates these with symptomatic behaviour. At our first milestone after 15 months we will evaluate our findings versus existing literature and we will then decide on alternative animal models if needed. In a second work package we will challenge the animal model with glutamate-altering drugs, known to aggravate or ameliorate human OCD symptoms, in order to more specifically pinpoint a target region for neuromodulation (second milestone; mid-term). We can always fold back to targeting the nucleus caudatus. The knowledge generated (neurobiology-WP1 and target region-WP2) will then be applied in a third work package to investigate repetitive Transcranial Magnetic Stimulation (rTMS) versus gold standard intra-cortical pharmacological modulation and Deep brain Stimulation (DBS). SUMMARY: we want to exploit multimodal and multiprobe molecular imaging to investigate the neuropathophysiology of OCD in an animal model and to evaluate novel neuromodulation treatments which we miniaturized for use in rodents.

Researcher(s)

• Promoter: Staelens Steven
• Fellow: Servaes Stijn

Research team(s)

Project type(s)

• Research Project

Abstract

This research project aims to improve the predictive value of preclinical animal studies through the implementation of small animal PET imaging (microPET). By employing transgenic mouse models that recapitulate certain pathological hallmarks of Alzheimer Disease we will validate and optimize a number of non-invasive biomarkers for disease monitoring.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Dedeurwaerdere Stefanie
• Fellow: Waldron Ann-Marie

Research team(s)

Project type(s)

• Research Project

Abstract

The main objective of this project is to improve the tumor targeting capability and pharmacokinetics of duramycin and RGD radiotracers using conjugation to POX for in vivo therapy evaluation in hypoxic and irradiated non small cell lung cancer. The use of a radiotracer with a better pharmacokinetic profile will result in better tumor/background ratio and faster differentiation between effective versus non-effective therapy thus in more efficient and cost-reducing personalized medicine.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Vangestel Christel
• Co-promoter: Wyffels Leonie

Research team(s)

Project type(s)

• Research Project

Abstract

We propose a novel hypothesis for the development of PTE with a central role for ECM modulating components MMP-9 and uPA. TBI results in blood-brain barrier disruption, hyperexcitability and primary damage triggering repair mechanisms such as modulation of the ECM by proteases MMP-9 and uPA. These alterations in ECM proteases MMP-9 and uPA, followed by brain inflammation, induce abnormal synaptic remodeling and epileptogenesis, ultimately leading to PTE.

Researcher(s)

• Promoter: Dedeurwaerdere Stefanie
• Co-promoter: Staelens Steven
• Fellow: Missault Stephan

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

Abstract

The following main challenges and yet unknown biological aspects of Poxylation, that need to be addressed to demonstrate the safety as well as potential of Poxylation over Pegylation, will be the main objectives to establish the poxylation technology. Besides developing the poxylation technology, this initial project aims to develop synthetic strategies for poxylated therapeutics.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Wyffels Leonie

Research team(s)

Project type(s)

• Research Project

Abstract

Proteases are important drug targets and show increasing application as biomarkers for several diseases. Non-invasive imaging of their proteolytic activity status in vivo offers tremendous potential. We will develop activity-based imaging probes targeting proteases with relevance in oncology and inflammation. These probes will be used in a two-step approach in which the pretargeting step is followed by bioorthogonal ligation with a PET label.

Researcher(s)

• Promoter: Augustyns Koen
• Co-promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

The main objective of this project is to develop a PET radiotracer for PDE7 imaging. The PDE7 inhibitors will be used as lead compounds. We selected two families of compounds to increase our chances to discover a suitable PDE7 radiotracer. The structure of the compounds will be modified for labelling with 11C. Precursors for radiolabeling and the 'cold' (non radioactive) standard compounds will be synthesized for radiotracer characterization and in vivo evaluation of PDE7 inhibitory potency and selectivity. The compounds showing the best potency (nanomolar IC50) and selectivity for PDE7 inhibition will be selected for radiolabeling. The next step will be the optimization of the radiosynthesis. The goal will be to obtain the products in a high radiochemical yield and in high radiochemical purity (> 95% for animal studies).

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Augustyns Koen
• Co-promoter: Staelens Steven
• Fellow: Thomae David

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Peeters Marc
• Co-promoter: Sijbers Jan
• Co-promoter: Staelens Steven
• Co-promoter: Van Der Linden Annemie

Research team(s)

Project type(s)

• Research Project

Abstract

Transcranial Magnetic Stimulation (TMS) is a treatment for various neurological disorders. We have developed a device and methods for the application of TMS in awake and freely moving small experimental animals. The project aims at performing indispensible evaluation tests and to develop a demonstrator, to support patent filing.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Wyckhuys Tine

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand a private institution. UA provides the private institution research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Wyffels Leonie

Research team(s)

Project type(s)

• Research Project

Abstract

The current project will follow the development of neuroinflammation together with functional brain integrity and behavioural outcome in a rodent model of maternal immune activation in vivo utilising state-of-the-art multimodal imaging biomarkers.This project will generate highly novel information about the contribution of neuroinflammation to the development of schizophrenia and its consequences for the functional integrity of the brain, and eventually provide a rationale for the implementation of novel disease-modifying strategies.

Researcher(s)

• Promoter: Dedeurwaerdere Stefanie
• Co-promoter: Staelens Steven
• Co-promoter: Timmermans Jean-Pierre
• Co-promoter: Van Der Linden Annemie

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

Abstract

The overall goal of this project is to improve the quantification of PET imaging through the development and use of innovative motion correction and image reconstruction techniques.

Researcher(s)

• Promoter: Staelens Steven

Research team(s)

Project type(s)

• Research Project

Abstract

Chronic neurological diseases such as epilepsy and schizophrenia are difficult to manage and severely disabling disorders. Moreover, they are putting a huge burden on our social health care system. Currently, there is no available therapy that effectively halts or retards the development or progression of these conditions. The more we learn, the more it becomes clear that these neurological diseases are extremely complex as they do not have a well-understood mechanism of action and perhaps diverging dysfunctions, with evolving temporal and spatial aspects, may contribute to the disease. Remarkably, the manifestation of both diseases is preceded by a seemingly "silent" or "latent" period of several years without any apparent symptoms. Interestingly, scientific research suggests that this could be related to a neuronal insult during a critical phase of life, which initiates a series of pathophysiological processes during the latent period. At current, little research has been directed to investigate the latent period. As in patients, the chronic stage of the disease is represented rather than the early stage, the human research endeavour has been limited due to the difficulty to set-up these type of long-term prospective studies. As a consequence, our understanding of the processes occurring during this critical phase of the development of the disorder is incomplete. For instance, it is unknown what factors contribute to the phenomenon that only a subgroup of individuals will eventually be affected by the disorder. A better insight in these events could potentially lead to early identification of patients at risk. It has been speculated that neuroinflammation plays an important role in the reorganisation of the neuronal network after the occurrence of a traumatic event. The current project will follow the development of neuroinflammation together with the investigation of the functional integrity of the brain in laboratory animals utilising imaging biomarkers. The recent advances in dedicated in vivo imaging techniques for small animal brain imaging, such as positron emission tomography (PET), allow scientist for the first time to conduct basic research in a non-invasive and longitudinal manner, facilitating translation of knowledge from bench side to clinical application. This study will add very important new information about the contribution of neuroinflammation to the development of neurological disorders such as epilepsy and schizophrenia, its consequences for the functional integrity of the brain and whether these biomarkers could contribute to the early identification of patients as risk. Non-invasive imaging using biomarkers is an upcoming and promising new approach, which clearly allows for translation of applications to the clinic. The outcomes of this research will inform clinical practice, particularly providing rationale for the implementation of potentially neuroprotective strategies to slow down or halt this degeneration, as well as potentially providing a method to assess the biological efficacy of prospective new therapies prior to the institution of expensive human trials.

Researcher(s)

• Promoter: Dedeurwaerdere Stefanie
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Staelens Steven

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

Abstract

Given the demographic aging, research in molecular imaging has a large social support and bearing. Moreover, the successful miniaturization of (S)PE(C)T cameras these past three to five years caused a major breakthrough for small animal imaging. Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for research and have entered the preclinical arena. These new imaging systems permit researchers to noninvasively screen animals for pathologies, to use various cell lines in drug and tracer development, to monitor disease progression and also response to therapy. Considerable benefits are the in vivo nature of these small animal imaging experiments enabling longitudinal studies with the animal acting as its own control, the robustness, less labour intensive biodistributions, and less sacrification of laboratory animals. This benchfee (if granted) will be applied for an integrated translational molecular imaging program for UA thereby initiating fundamental science driven by clinical questions and enabled through these preclinical research tracks. This approach efficiently closes the feedback loop to the hospital ultimately resulting in improved patient comfort.

Researcher(s)

• Promoter: Staelens Steven
• Fellow: Staelens Steven

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Given the demographic aging, research in molecular imaging has a large social support and bearing. Moreover, the successful miniaturization of (S)PE(C)T cameras these past three to five years caused a major breakthrough for small animal imaging. Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for research and have entered the preclinical arena. These new imaging systems permit researchers to noninvasively screen animals for pathologies, to use various cell lines in drug and tracer development, to monitor disease progression and also response to therapy. Considerable benefits are the in vivo nature of these small animal imaging experiments enabling longitudinal studies with the animal acting as its own control, the robustness, less labour intensive biodistributions, and less sacrification of laboratory animals. This benchfee (if granted) will be applied for an integrated translational molecular imaging program for UA thereby initiating fundamental science driven by clinical questions and enabled through these preclinical research tracks. This approach efficiently closes the feedback loop to the hospital ultimately resulting in improved patient comfort.

Researcher(s)

• Promoter: Staelens Steven

Research team(s)

Project website

Project type(s)

• Research Project