Projects

Abstract

Cancer-associated fibroblasts (CAFs) are a group of tumor stromal cells typically associated with cancer growth and metastasis. These CAFs show high expression of the fibroblast activation protein (FAP) on the cell membrane. Due to the selective FAP expression and cancer-specific distribution, CAFs have emerged as a promising cancer diagnostic marker and an attractive therapeutic target. The recent success of FAP-targeted positron emission tomography (PET) radiotracers, led to more research for radiopharmaceutical therapies to the this protein. Furthermore, a FAP-targeted approach gives the opportunity to use a using the same ligand for both imaging of the expression of FAP and to target it with a radionuclide therapy (theranostics), to enables a personalized cancer treatmentmedicine approach. However, the current FAP ligands show suboptimal tumor-residence time, which is of particular importance for radionuclide therapy. Therefore, in this application we aim to develop novel FAP-targeting radiotheranostics. The radiotracers will be first evaluated in vitro to assess FAP selectivity and activity, followed by in vivo imaging and therapy using a human cancer mouse model.

Researcher(s)

• Promoter: Elvas Filipe
• Co-promoter: Van den Wyngaert Tim
• Co-promoter: Van Der Veken Pieter
• Fellow: Vanermen Maarten

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Radioligand therapy has recently received renewed attention as promising treatment option to improve cancer patient outcome. Compared to conventional cancer treatments, this strategy involves a more specific targeting of therapeutic radionuclides to the tumor, which aims to increase treatment efficacy. Despite recent progress, currently available treatments show insufficient tumor killing and normal tissue toxicity, and we hypothesize that a pretargeted click-to-release (C2R) strategy can bridge this gap. Within this strategy, we propose to explore Fibroblast Activation Protein (FAP) inhibitors as tumor targeting vectors, to deliver a therapeutic radionuclide fragment intracellularly using cell permeable, cleavable transcyclooctene (dcTCO) constructs and compare it with conventional dTCOs. To reinsure intracelular release, after C2R, we designed new structures containing an RGD peptide (with integrin αvβ3 binding specificity). Our molecular constructs also aim to prevent FAP efflux, by using a guanidinium and nicotinoyl residualizing groups. This project will evaluate the reactivity, in vitro stability, logD and radiochemical yield of the new molecules, and the C2R efficiency of the dcTCOs. A FAP inhibitor (dimer) will be weaponized with a tetrazine handle to be the targeting vector and biorthogonal pair of these new constructs, and it's affinity and selectivity will be evaluated in vitro, against other proteases. The dcTCOs and dTCOs with better reaction kinetics and C2R efficiency (dcTCOs) will be selected for the development of 18F- and 125I-radiolabeled probes. The celular uptake and internalization will be evaluated on tumor cells (FAP positive cells, integrin αvβ3 positive cells, both FAP and αvβ3 positive). This project is a innovative strategy to improve the radiation dose delivered to the tumor and improving treatment outcome, while reducing radiotoxicity and achieving better treatment tolerability.

Researcher(s)

• Promoter: Elvas Filipe
• Co-promoter: De Meester Ingrid
• Co-promoter: Van Der Veken Pieter
• Fellow: Da Silva Gustavo

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Ondanks vooruitgang in kankerbehandelingen blijft er een hoge klinische nood bestaan aan nieuwe therapieën om de overleving te verbeteren. Vergeleken met chemotherapie zijn gerichte radiofarmaca gekoppeld aan diagnostische of therapeutische radionucliden veelbelovend om de therapeutische werkzaamheid te verbeteren met minder toxiciteit. De CD70-CD27-as is abnormaal geactiveerd in vele tumoren (vb. niercelcarcinoom) en betrokken bij immuunontwijking en tumorprogressie. De beperkte expressie van CD70 in normale weefsels maakt dit een aantrekkelijk doelwit voor op monoklonale antilichamen (mAb) gebaseerde therapieën. Echter, de huidige beschikbare behandelingen gericht tegen CD70 hebben een onvoldoende tumordodend vermogen laten zien, en wij schuiven de hypothese naar voor dat radioimmunotherapie betere resultaten kan bereiken met behulp van een theranostische benadering. Onder het theranostisch paradigma "wat je ziet is wat je behandelt", zullen wij CD70-gerichte radiofarmaca ontwikkelen met behulp van het krachtige theranostische radionuclide paar 64Cu/67Cu voor diagnose met positron emissie tomografie (PET) en radionuclide therapie. Met dit paar kunnen diagnostische (d.w.z. voor patiëntselectie en behandelingsplanning) en therapeutische (d.w.z. voor kankerbehandeling en dosimetrie na de behandeling) radiofarmaca worden gemaakt die alleen verschillen in het isotoop van hetzelfde element. Hierdoor is er een identiek biochemisch gedrag en farmacokinetiek, in tegenstelling tot vele momenteel gebruikte theranostische middelen. Hiertoe onderzoeken wij een nieuwe intracellulaire pretargeted radioimmunotherapie (PRIT) strategie waarbij gebruik wordt gemaakt van radiogelabelde transcyclooctenen (TCO) en mAb-tetrazine (Tz) conjugaten. Deze strategie is gericht op het verbeteren van CD70 targeting door het creëren van stabiele en reactieve mAb-Tz conjugaten en nieuwe cel-permeabele radiogelabelde TCO structuren met hoge stabiliteit en reactiviteit. Vervolgens zullen we de dosering, het toedieningsschema en de stralingsdosimetrie van de anti-CD70-mAb-Tz en 64Cu/67Cu-NOTA-TCO optimaliseren voor in vivo tumor pretargeting. Ten slotte zullen we een eerste proof-of-concept in vivo preklinische studie uitvoeren om een therapeutisch signaal te detecteren van onze PRIT-benadering.

Researcher(s)

• Promoter: Van den Wyngaert Tim
• Co-promoter: Elvas Filipe
• Fellow: Yu Quanyi

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Surgical anterior cruciate ligament (ACL) reconstruction using tendon graft is the standard to treat ACL injuries. However, little is known about the maturation process of human ACL graft and the role of adjacent structural abnormalities herein. There currently exists a high clinical need for improved noninvasive objective measures of ACL graft properties to help inform return to high-demand activities. Next to anatomical magnetic resonance imaging (MRI), quantitative MRI (qMRI) techniques, such as T2* relaxometry and diffusion tensor imaging (DTI), have gained interest for musculoskeletal imaging. qMRI provides objective measures of biophysical tissue properties that allow for monitoring of tissue microstructure. Despite its demonstrated potential to provide biomarkers of ACL graft maturation, standard qMRI suffers from low resolution and long scan times, impeding clinical validation. To improve the trade-off between signal-to-noise ratio, resolution and scan time, we propose a super-resolution reconstruction (SRR) framework for anatomical MRI and qMRI of the knee that will overcome the current limitations for biomarker identification. In this project, we will develop SRR qMRI for T2* relaxometry and DTI of the knee and provide further insight into the condition of maturing ACL graft in patients before return to play. SRR qMRI may also improve our ability to evaluate the effectiveness of additional treatments to accelerate ACL graft maturation.

Researcher(s)

• Promoter: Van Dyck Pieter
• Co-promoter: Jeurissen Ben

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Lung cancer is the leading cause of cancer death, worldwide and in Belgium. Lung cancer screening (LCS) with low-dose Computed Tomography (LDCT) has been shown to reduce lung cancer specific mortality up to 26% in a high-risk population of current and former smokers. Implementation of LDCT LCS is hence in progress in several European countries, including Belgium. Recruitment of the target group, which is not defined by age and sex but by risk of developing lung cancer, is different than other cancer screening programmes and faces several challenges and barriers to overcome. Our study will A/Prospectively investigate the accrual of eligible high-risk participants in 5 different cohorts of at-risk Flemish citizens: 1/approach by their general practitioner, 2/occupational physician, 3/tobaccologist, 4/a letter joined to their next coming invitation for breast or colon cancer screening and 5/approach of hard-to-reach socio-economic minorities through the Centers for Respiratory Health (Flemish Society of Respiratory Health and Tuberculosis-VRGT) B/Gain insight into the views of relevant stakeholders regarding best practices, barriers, and opportunities for successful implementation of a future lung cancer screening programme in Flanders.

Researcher(s)

• Promoter: Snoeckx Annemiek
• Co-promoter: Theuns Charlotte
• Co-promoter: Van Hal Guido

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Fibroblast activation protein (FAP) is a serine protease expressed on stromal cells of > 90% of all epithelial cancers, whereas its expression is almost undetected in normal tissues. In addition, FAP expression is highly restricted and transiently increased in adult tissues during wound healing, inflammation or fibrosis in activated fibroblasts. Among the stromal cells, cancer associated fibroblasts (CAFs) having a FAP-positive phenotype have been associated with poor prognosis in multiple cancers. The highly focal expression and cancer-specific distribution of FAP make this protein a promising cancer diagnostic marker and an attractive therapeutic target. Motivated by the success of FAP-targeted positron emission tomography (PET) radiotracers, FAP-targeted radiopharmaceutical therapies are currently heavily investigated. In addition, FAP-targeted radiopharmaceuticals offer the possibility of imaging diagnostics and targeted radionuclide therapy using the same ligand (theranostics), enabling personalized cancer treatment. However, the relatively rapid washout from the tumor and inadequate pharmacokinetics of current FAP ligands represents a major problem for radioligand therapy. Therefore, the goal of this application is to develop FAP-targeting radiotheranostics. Radiotracers will be evaluated in vitro to assess FAP activity and selectivity. Finally, a human cancer mouse model will be used to assess both imaging and therapeutic potential of our FAP- radiotracers. If successful, our strategy will help physicians select patients who can benefit from FAP-targeted radionuclide therapy.

Researcher(s)

• Promoter: Elvas Filipe
• Co-promoter: Van den Wyngaert Tim
• Co-promoter: Van Der Veken Pieter
• Fellow: Vanermen Maarten

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

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

Bone health equilibrium can be altered by disease and the use of medication. Antiresorptive drugs are frequently used and highly effective to prevent bone metastasis in patients with cancer. Yet, their use is associated with the occurrence of medication-related osteonecrosis of the jaw (MRONJ), a potentially debilitating side effect characterized by exposed necrotic bone in the oral cavity, infection, and pain Although research on advanced MRONJ lesions have been published, so far little is known on the early disease stages, the initial imaging features and potential preventive measures related to early detection and disease prediction. Likewise, radiological risk factors to identify a successful outcome or therapy resistance have not yet been described. Therefore, the main objective of this project is to build an automated prediction model (radiomics) to allow prediction of MRONJ induction and its response to treatment. This could be reached by the following subobjectives: 1. To identify the radiological and genetically predisposing factors to develop MRONJ 2. To describe risk factors influencing treatment outcome in patients with MRONJ In order to obtain the subobjectives, 2 studies will be carried out: o A prospective cohort study to follow-up patients at risk for MRONJ development enabling to identify risk factors. o A retrospective cohort study in patients MRONJ that underwent surgical or conservative treatment to identify radiological features associated with treatment

Researcher(s)

• Promoter: Van den Wyngaert Tim

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

The emerging trend in cancer therapy is to enhance cytotoxic immune response by activating cytotoxic cells to achieve effective killing of malignant cells and to reprogram myeloid cells toward an anti-tumor phenotype, representing the current foundations of cancer immunotherapies. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. But, despite impressive tumor effects and extended patient survival, not all patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. I aim to establish a strong Radiopharmacy research group addressing these needs, with a primary interest in developing radiopharmaceuticals for molecular imaging of biomarkers/targets that can contribute to the use of immunotherapy in the most effective way, maximizing the likelihood of response. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations due to the intrinsic tumor heterogeneity and the latter are invasive. In addition, conventional imaging modalities have proven challenging to monitor early responses to cancer immunotherapy and fail to provide any biological insight of the immune cells. To overcome some of these issues, the use of a noninvasive, sensitive, and quantitative molecular imaging technique such as positron emission tomography (PET) using specific radiotracers can provide non-invasive and longitudinal whole-body monitoring of immune responses. Hence, I have put three strategies forward. First, the development of radiopharmaceuticals targeting cysteine protease activity. Given the relevance of their immunoregulatory roles, imaging of cysteine protease activity may prove useful for the design of optimized immunotherapies. Second, the use B-cell maturation antigen (BCMA)-targeted immunoPET to monitor tumor burden, interrogate target availability and assess treatment response of patients with multiple myeloma. Third, immunoPET imaging of the co-stimulatory CD27/CD70 pathway is expected to shed light on the heterogeneous target expression observed between patient tumors, thereby increasing the success of cancer immunotherapies with immunomodulatory monoclonal antibodies and paving the way for novel therapeutic approaches. The experimental set-up will be determined in a project-by-project manner but will typically involve the design and (radio-)chemical synthesis of radiopharmaceuticals, as well as in vitro and in vivo validation strategies in relevant tumor cells and mouse models of cancer.

Researcher(s)

• Promoter: Elvas Filipe
• Fellow: Elvas Filipe

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Caspases are well known for their role as executioners of apoptosis. However, recent studies have suggested that these lethal enzymes also have important non-canonical roles in the activation and proliferation of T cells. Effective antitumor immune response is based on the ability of T cells to recognize and destroy cancer cells, for which activation of caspase-3 (c-3) is key. Therefore, the assessment of tumor response based upon the activation of c-3 following immunotherapy, may represent a promising strategy for early prediction of therapy outcome. The current set of c-3-targeted positron emission tomography (PET) radiotracers does not provide adequate resolution and signal-to-noise ratio to precisely visualize c-3 activity during the course of immunotherapy. In addition, monitoring of CAR T-cell trafficking to the tumor site is still not possible in cancer patients. Therefore, the goal of this application is to develop PET radiotracers for selectively imaging c-3 and to investigate their value for prediction and evaluation of responses to immunotherapy. We propose to use novel c-3 specific cell-permeable activity-based probes to visualize dying tumors following immunotherapy, and c-3 specific cleavable metabolic probes for bioorthogonal monitoring of T cell activation and trafficking to tumor cells. Probes will be evaluated in vitro to assess c-3 affinity and selectivity, and in vivo using cancer xenograft models treated with immunotherapy for response evaluation.

Researcher(s)

• Promoter: Elvas Filipe
• Fellow: Lauwerys Louis

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Colorectal cancer (CRC) is one of the major health concerns in the western world and the second leading cause of cancer death in the USA. While the availability of novel active agents has improved the prognosis of patients with CRC, patients with metastatic disease have a 5-year overall survival rate of only 13%. The current treatment paradigm consists of the subsequent use of cytotoxic chemotherapy and/orselected targeted agents. Objective and accurate evaluation of the tumor response to therapy represents one of the biggest challenges in oncology. An early assessment of therapeutic ineffectiveness will avoid treatment related toxicity to the patient and could lead to improved survival by allowing earlier treatment intensification, discontinuation of ineffective therapy, or initiation of second-line therapy. In today's clinical practice treatment response evaluation is primarily based on anatomical imagingand focuses on the volumetric and morphometric assessment of the tumor. Unfortunately, it usually takes a few weeks to months after start of the therapy before morphological changes become apparent. In that time span, non-responding patients are suffering from avoidable side-effects and can possibly be subject to disease progression. Consequently, there is a growing demand for non-invasive molecular imaging biomarkers that allow early monitoring of treatment efficacy. Phosphatidylethanolamine (PE), expressed only on apoptotic and dead cells, provides an attractive molecular biomarker for the detection of cell death. Duramycin, a naturally occurring peptide antibiotic that binds specifically to PE, has been successfully used as a probe for the imaging of cell death in several animal models.The main goals of this project are to conduct Phase 0 and early Phase I clinical studies of the proprietary imaging probe, [99mTc]duramycin, to ascertain its safety and ability to detect cancer therapyinduced cell death. By comparing a [99mTc]duramycin SPECT scan obtained early after onset of the therapy to a pretreatment scan clinicians should be able to distinguish responders versus non-responders sooner than with anatomical methods.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Elvas Filipe

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). 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

Preclinical brain positron emission tomography (PET) is performed using anaesthetics to immobilize the animal. However, it has been shown that anaesthetics can influence brain function and the uptake of several PET tracers. To circumvent the use of anaesthesia, methods that track the motion of the animal head during the PET scan have been developed, which aid subsequent motion correction of the brain PET data. These methods rely on optical tracking cameras or on markers attached on the animal head to track the head motion. Therefore, the tracking procedure requires additional setup procedures in addition to the PET scan itself. To improve practicality and to reduce the additional setup to perform scans of awake rodents the minimum, we will validate and optimise a rodent head data-driven tracking technique in this project. This method requires no additional setup in addition to the PET scan, since the motion tracking is performed using the acquired PET data. Additionally, a torso motion tracking will be validated and optimised to perform heart motion correction reconstruction. The heart image can then be used to obtain the image derived input function to perform improved quantification with kinetic modelling. Rat and mice scans will be performed with different PET tracers to obtain data with different brain and body distributions, as well as different noise characteristics, to optimise the tracking algorithms. The methods developed here will serve to improve practicality of awake PET rodent scans, therefore facilitating adoption of the technique by the wider PET preclinical community. By circumventing the use of anaesthetics and their confounding effects on the animal physiology, translation of preclinical PET results to the clinic will be improved.

Researcher(s)

• Promoter: Miranda Menchaca Alan

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Fibroblast activation protein (FAP) is a serine protease expressed on stromal cells of > 90% of all epithelial cancers, whereas its expression is almost undetectable in normal tissues. In addition, FAP expression is highly restricted and transiently increased in adult tissues during wound healing, inflammation, or fibrosis in activated fibroblasts. The highly focal expression makes FAP a promising diagnostic marker and an attractive therapeutic target, not only in cancer, but also in fibrotic and cardiovascular diseases. UAntwerp has an approved patent for the only highly potent, selective and orally bioavailable small molecule inhibitors of FAP known to date (US9346814 and EP2804859). One of the compounds in this patent (UAMC1110) has received widespread attention as the structural basis for FAP-targeted positron emission tomography (PET) radiotracers and FAP-targeted radiopharmaceutical therapies, which are currently heavily investigated and in high demand by the pharmaceutical industry. Also, at UAntwerp, research is ongoing that aims at producing UAMC1110 derivatives, with main applications in the in vitro diagnostics field. In addition, in the scope of a former IOF-POC project the applicants of this proposal have collaborated on the discovery of 18F-labeled UAMC1110 derivatives that can be used as PET diagnostics in oncology, fibrosis and related domains, and in cardiovascular disease. Recently, we have developed a small library of 18F-labeled probes that show promising stability, pharmacokinetics and tumour-targeting properties in human glioblastoma cancer xenografts. Based on this preliminary data a patent application has been filed. However, there is still room for improvement by reducing the accumulation of these probes in non-targeted organs, which is especially relevant in the context of radionuclide therapy. Through structural optimization (increasing the polarity of the probes), this POC project aims to expand this library and deliver compounds having high metabolic stability and less or no accumulation in liver and gastrointestinal tract. Following the proof-of-concept, these optimized probes will be included in the patent that will be filed in early June 2022, which should strengthen the industrial development of these probes as PET-diagnostics and theranostics.

Researcher(s)

• Promoter: Elvas Filipe
• Co-promoter: De Meester Ingrid
• Co-promoter: Stroobants Sigrid
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Lung cancer causes a large mortality, worldwide and in Flanders, with 3822 cases in 2016. The only technique with proven mortality reduction is lung cancer screening (LKS) with CT scans. In 2020, a mortality reduction of 26% (men) and 41% (women) was measured in the Dutch-Belgian "NELSON" study. The Flemish 'Task Force Lung Cancer Screening' therefore brings together experts to design and subsequently support an LKS program for population groups where this improvement can be continued. All (expected) questions from the responsible Flemish government must be answered. With this project, radiologists and physicists from the Task Force want to find adequate answers to the following questions: what is the radiation risk associated with the CT scans? Can imaging be optimized for even lower X-ray doses? How are computer algorithms for detecting and measuring cancers performing? The greatest challenge is to develop new test methods in a world with rapidly changing technology - e.g. artificial intelligence. Three university groups will combine their expertise with (1) risk assessment, (2) evaluation of clinical image quality and (3) computer-aided detection and characterization of cancer. All new techniques and test criteria will be bundled in a unique test protocol to assess and optimize the quality of each CT protocol or computer algorithm for LKS.

Researcher(s)

• Promoter: Snoeckx Annemiek

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Daniele Bertoglio graduated with the highest honours in Pharmaceutical Biotechnology at the University of Bologna, Italy in November 2014, after performing his master thesis at the Robert Wood Johnson Medical School in New Jersey, USA. Immediately after, he began working as a Ph.D. researcher in Medical Sciences at the University of Antwerp in December 2014 and successfully obtained an FWO Ph.D. fellowship in 2015. His doctoral studies exploited the use of positron emission tomography (PET) imaging as a prime non-invasive in vivo tool for direct assessment of alterations in several molecular targets in preclinical models of Huntington's Disease (HD) to characterize non-invasively dynamic molecular changes occurring at key stages of HD progression. His research pioneers the field of PET imaging of mutant huntingtin (mHTT) aggregates in active preparation for human biomarker studies in longitudinal follow-up of patients and clinical candidate therapies, providing an outstanding contribution to the field of Molecular Imaging for HD. His research included multimodality imaging techniques as well as robust post-mortem assessment to unravel novel candidate markers for HD, which have resulted in excellent contributions in high-impact peer-reviewed international journals and the Ph.D. in Medical Sciences defended at the University of Antwerp in November 2019. His scientific interest and passion for preclinical neuroimaging led him to pursue a second Ph.D. in Biomedical Sciences investigating the process of epileptogenesis in preclinical models of acquired epilepsy using different studies combining magnetic resonance imaging (MRI) and PET imaging which was successfully defended at the University of Antwerp in June 2021. In addition, Daniele obtained an FWO postdoc position, and he is working as a postdoctoral researcher at MICA, University of Antwerp. He uses various translational neuroimaging tools to quantify structural, functional, and molecular changes in preclinical models of neurological diseases, focusing on Huntington's disease, temporal lobe epilepsy, and spinal cord injury. His research applies state-of-the-art small animal neuroimaging techniques, including MRI and PET imaging, to identify novel candidate biomarkers to monitor disease progression, predict disease outcome, and evaluate the efficacy of innovative therapeutic approaches. To date, Daniele has co-authored a total of 23 original peer-reviewed publications in international journals, of which 14 as the first author, and contributed to 2 book chapters.

Researcher(s)

• Promoter: Bertoglio Daniele

Research team(s)

• Molecular Imaging and Radiology (MIRA)
• Bio-Imaging lab

Project type(s)

• Research Project

Abstract

One of the missions of BELNUC is to promote research and development by young individuals. To that end, BELNUC is calling for applications for one travel award (€10.000) to support a promising young researcher to realize an internship abroad.

Researcher(s)

• Promoter: Van den Wyngaert Tim

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Traumatic Brain Injury (TBI) is a sudden damage in the brain caused by an external force to the head. There are 50 million TBI cases worldwide every year, with over 2.5 million people in Europe. Mild TBI (mTBI) cases account for over 85% of the head injuries. In up to 40% of the cases, recovery from mTBI may be incomplete, with patients having persistent motor and psychological impairment for months to years after injury. Magnetic resonance imaging (MRI) is a helpful tool for documenting the extent of brain damage and is routinely applied in clinical practice. However, patients with mTBI often do not show abnormalities on conventional MRI, despite changes in behavior or cognitive deficits. This observation indicates that some microstructural changes in the brain cannot be detected by conventional MRI, but may be important determinants of a patient's clinical outcome. A number of studies using more advanced diffusion MRI (dMRI) have reported changes in diffusion parameters associated with meaningful clinical measures, such as cognitive and functional impairment in mTBI. Currently, radiologists and neurologists cannot predict the outcome of mTBI patients based on conventional MR images. However, recent developments in machine learning methods have shown promise for improving outcome prediction by combining multiple clinical parameters. We have previously explored Support Vector Machine learning algorithms for outcome prediction of mTBI patients based on voxel-wise analysis of FLAIR, SWI, FA and MD images. In the next step, we aim to explore Deep Learning algorithms for outcome prediction. Deep learning is facilitated by neural networks that mimic the neurons in the human brain, which autonomous learns from data. Specifically, we will implement a convolutional neural networks (CNN) based methods for outcome prediction in mTBI, using conventional and diffusion MRI from the multi-site CENTER-TBI project. Good ve\rsus incomplete recovery will be dichotomised using the Extended Glasgow Coma Scale (GOSE) score, evaluated at 6 months after injury. Ultimately, improved prediction of mTBI outcome would help to stratify patients and better organize the management of mTBI patients with poor outcome.

Researcher(s)

• Promoter: Van Dyck Pieter

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 mutant huntingtin (mHTT). Patients with HD exhibit progressive motor and cognitive decline, and development of psychiatric symptoms. Pathological features of HD include wide-spread progressive accumulation of mHTT, selective neurodegeneration, and forebrain atrophy. The synaptic vesicle glycoprotein 2A (SV2A) is a vesicle membrane protein expressed ubiquitously in synapses of the brain, involved in neurotransmitter release. SV2A can be used as a proxy to measure synaptic density in vivo using the radioligand [11C]UCB-J and positron emission tomography (PET). Based on our in vivo [11C]UCB-J PET imaging and in vitro [3H]UCB-J autoradiography findings in HD mice, demonstrating SV2A decline, we hypothesize the levels of SV2A to be decreased in patients with HD as a direct effect of mutant huntingtin accumulation as well as by the consequent neurodegeneration occurring with disease progression. Thus, the objective of this project is to provide evidence for the clinical significance of SV2A as a candidate biomarker in patients with HD in comparison to age- and gender-matched healthy non-demented subjects using in vitro autoradiography and immunohistochemistry in post-mortem samples from patients with HD and healthy subjects. The knowledge derived from this project will not only contribute to supporting the preclinical outcomes, filling the gap between preclinical and clinical findings, but it will represent a significant contribution in supporting SV2A as a candidate imaging biomarker for disease progression to be investigated in longitudinal SV2A PET imaging studies in patients with HD.

Researcher(s)

• Promoter: Bertoglio Daniele

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

Caspases are well known for their role as executioners of apoptosis. However, recent studies have suggested that these lethal enzymes also have important non-canonical roles in the activation and proliferation of T cells. Effective antitumor immune response is based on the ability of T cells to recognize and destroy cancer cells, for which activation of caspase-3 (c-3) is key. Therefore, the assessment of tumor response based upon the activation of c-3 following immunotherapy, may represent a promising strategy for early prediction of therapy outcome. The current set of c-3-targeted positron emission tomography (PET) radiotracers does not provide adequate resolution and signal-to-noise ratio to precisely visualize c- 3 activity during the course of immunotherapy. In addition, monitoring of CAR T-cell trafficking to the tumor site is still not possible in cancer patients. Therefore, the goal of this application is to develop PET radiotracers for selectively imaging c-3 and to investigate their value for prediction and evaluation of responses to immunotherapy. We propose to use novel c-3 specific cell-permeable activity-based probes to visualize dying tumors following immunotherapy, and c-3 specific cleavable metabolic probes for bioorthogonal monitoring of Tcell activation and trafficking to tumor cells. Probes will be evaluated in vitro to assess c-3 affinity and selectivity, and in vivo using cancer xenograft models treated with immunotherapy for response evaluation.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Augustyns Koen
• Fellow: Elvas Filipe

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

In this project, a miniaturized injection device will be developed. The injection device will be carried by a rat and will be operated by remote control to perform an intravenous bolus injection (0.5 ml / min) in the rat via a catheter in the jugular vein. The injection device will be used for the injection of a radio-tracer into the animal while being in the scanner during the dynamic brain imaging of awake, free-running animals. Since access to the scanner is limited due to the small bore size, the injection must be delivered through a miniature injection device that can be carried by the rat. The aim of the project is to be able to extend our previously developed methodology of brain imaging in free-running animals to dynamic scans where the animal is injected while it is in the scanner. Previously, our imaging in awake animals was only performed after the animals were injected outside the scanner. However, these post-injection scans are less useful for quantitative biomedical research in neuroscience. By developing the automated injection device, we will be able to perform the more relevant dynamic PET scans in free-running animals. In this way we can scan free running animals and we can avoid the influence of anesthesia (as used for PET imaging of small animals) on the brain and thus the measurement results. The usability of the injection device will be demonstrated in a dynamic PET test-retest study in rat in which dopamine receptors will be visualized using [11C]raclopride, a D2 receptor antagonist.

Researcher(s)

• Promoter: Verhaeghe Jeroen

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Flanders BioImaging (FBI) is an interuniversity consortium dedicated to biomedical imaging and advanced light microscopy, that was set up to integrate, optimize, rationalize and coordinate available imaging infrastructure in Flanders.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: De Vos Winnok

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

The receptor activator of the nuclear factor κ B ligand (RANKL) is an important component in carcinogenesis, specifically in the maintenance of self-renewal of cancer stem cells and up-regulation of anti-apoptotic pathways. In the tumor microenvironment, RANKL expression by tumor cells is associated with poor prognosis and more aggressive disease, of amongst others head-and-neck and breast cancer; two malignancies with poor outcome and in urgent need of better prognostic biomarkers and treatment options. However, current research on RANKL is hampered by the lack of a non-invasive biomarker of RANKL expression and dynamics in the tumor microenvironment. We propose a novel use of immuno-positron emission tomography (PET) by radiolabeling the anti-RANKL monoclonal antibody denosumab as longitudinal non-invasive imaging biomarker. The current proposal of this innovative approach includes developing and validating the labeling procedure, establishing the preclinical mouse models, evaluating the biodistribution, and biomarker validation in xenograft and metastatic mice models of oral squamous cell cancer (OSCC) and triple-negative breast cancer (TNBC). To this end, tumor models will be created with high and low RANKL expression, as well as modulation of tumor-derived RANKL using pharmacological intervention. Both a long (zirconium-89) and a short (gallium-68) half-life PET emitter will be studied to facilitate translation to human applications. Novel techniques will have to be developed to optimize antibody labeling with specific application to RANKL imaging, to derive unique immuno-PET imaging signatures of RANKL expression, and to establish the predictive value of this new biomarker. This challenging project will contribute to the understanding of the heterogeneity of RANKL expression, the dynamics of RANKL binding, and impact of RANKL-directed treatment on the tumor microenvironment. This can ultimately impact and improve the selection of patients in trials of RANKL-directed cancer treatments in these two frequent and aggressive diseases (i.e. OSCC and TNBC).

Researcher(s)

• Promoter: Van den Wyngaert Tim
• Fellow: Dewulf Jonatan

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Apoptosis or programmed cell death plays a major role not only in the pathogenesis but also in the treatment of cancer. In recent years, a variety of novel cell death inducing molecular cancer therapies have entered the clinic. Although many demonstrated their potential as effective treatment options in several types of cancer, costs to patients and the healthcare system are often staggering. Moreover, most anti-cancer treatments are linked to toxicity to healthy tissues. Early objective and accurate evaluation of tumor response to therapy is therefore of great importance. Tumor response assessment based upon the molecular effects of therapies, such as cell death induction, is a promising strategy for early prediction of therapy outcome. The availability of a radiotracer for positron emission tomography (PET) imaging of cell death could offer clinicians a tool to early after onset of treatment predict individualized responses in patients, and aid in personalized and cost-reducing patient care. Activation of caspase-3 and exposure of phosphatidylethanolamine (PE) represent key biomarkers for apoptosis. Currently no caspase-3 selective nor PE targeting PET radiotracers are available. This project therefore aims at developing novel caspase-3 selective and PE targeting radiotracers for PET imaging of cell death. Both cell death targeting strategies will be compared for early in vivo evaluation of response to therapy (immunotherapy and multi-kinase inhibitor treatment in preclinical models of colorectal cancer).

Researcher(s)

• Promoter: Stroobants Sigrid
• Promoter: Wyffels Leonie
• Co-promoter: Elvas Filipe
• Co-promoter: Van Der Veken Pieter
• Fellow: Beroske Lucas

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Patients with major depression benefit from therapeutic sleep deprivation. The causality of this clinically effective therapeutic measure is unknown; there is particularly only rare information about the underlying molecular mechanisms. We hypothesize that prolonged wakefulness is associated with an increase in synaptic strength, and that the synaptic dysregulation is affecting long term potentiation in patients with major depression. The aim of the project is to examine the synaptic basis of the antidepressant effect of therapeutic sleep deprivation by Positron Emission Tomography (PET) imaging of the synaptic vesicle protein 2A (SV2A) as a measure of synaptic density in patients and healthy subjects as well as animal models of depression. Since both anesthesia and sleep are subject to compromise biologically valid outcomes when studying the synaptic basis of therapeutic sleep deprivation, a fully quantitative PET imaging method for awake animals will be developed. We are convinced that synaptic density determined with PET has the power to become an indicator for the success of therapeutic sleep deprivation and thus providing means for future stratifications of different therapies in major depression. Identifying and understanding the mechanisms that mediate the effects of sleep restriction is necessary to develop effective interventions. This project will test a model that can be used to improve schedule design.

Researcher(s)

• Promoter: Verhaeghe Jeroen

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Cell death is a fundamental biological process. As different therapies may result in activation or inhibition of cell death, there is a need for imaging techniques that can identify cell death during patient treatment. The development of molecular probes targeting cell death biomarkers are key. The exposure of phosphatidylethanolamine (PE) in the cell membrane is an important biomarker for cell death. Specific in vivo positron emission tomography (PET) imaging of PE could therefore aid in the assessment of early response to cancer therapy, preventing exposure of patients to needless toxicity. Duramycin is a small peptide that binds to PE with high affinity and selectivity. The aim of the current work is the development of [18F]duramycin as a novel radiotracer for noninvasive PET imaging of cell death. Following optimization of radiochemistry, the tracer will be characterized to assess cell death binding and target selectivity, stability and pharmacokinetic behavior. Clinical applicability of the probe for therapy response assessment will be evaluated in well characterized cancer xenograft models treated with regorafenib, a multi-kinase inhibitor.

Researcher(s)

• Promoter: Elvas Filipe

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Cell death is a fundamental biological process. As different therapies may result in activation or inhibition of cell death, there is a need for imaging techniques that can identify cell death during the course of patient treatment. The development of molecular probes targeting cell death biomarkers are key. Caspase-3 activation and exposure of phosphatidylethanolamine (PE) in the cell membrane are important biomarkers for cell death. Selective in vivo positron emission tomography (PET) imaging of caspase-3 and PE could therefore aid in the assessment of early response to cancer therapy, preventing exposure of patients to needless toxicity. Recently, the use of unnatural amino acids in the caspase-3 recognition sequence and the modification of prime probe regions were described to be efficient strategies to design caspase-3 selective probes. Duramycin is a small peptide that binds to PE with high affinity and selectivity. The aim of the current work is the development of 18F-duramycin and 18F-labeled caspase-3 selective probes for noninvasive PET imaging of cell death. Following optimization of radiochemistry, the probes will be characterized to assess cell death binding and target selectivity, stability and pharmacokinetic behavior. Clinical applicability of the different probes will be evaluated in well characterized cancer xenograft models treated with targeted therapy or immunotherapy and compared to the clinical gold standard 18F-FDG for therapy response evaluation.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Augustyns Koen
• Fellow: Elvas Filipe

Research team(s)

• Molecular Imaging and Radiology (MIRA)

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

Traumatic Axonal Injury (TAI) is now considered to be a frequent and important injury in all severities of traumatic brain injury (TBI). The global aim of TAI-MRI is to develop a novel classification for TAI using data from multimodal MRI and to determine its clinical value for the characterization of injury severity and prediction of outcome. This project, involving 4 partners, will use MRI datasets obtained early after injury (including clinical and advanced MRI) from two local studies (The Trondheim and Cambridge TBI studies: ~580 patients) and the EU-funded multicenter CENTER-TBI study (~800 patients). TAI-MRI will thus be the largest MRI study worldwide. These datasets comprise a comprehensive collection of acute phase variables reflecting the severity of injury with the possibility to adjust for confounding variables and outcome measures at multiple time points during the first year. Several training sets will be used for model selection. Automated methods involving deep learning techniques will be developed and used for lesion mapping in combination with manual assessments. Methods for computer aided diagnosis (CAD) will be refined and validated, and analyses will determine which aspects of CAD based evaluation could replace expert clinical evaluation by radiologists. Finally, this novel MRI classification system will be validated in the large CENTER-TBI dataset. An improved MRI-based classification system of TAI will provide both a better assessment of injury severity in the acute phase and better outcome prediction. Recent advances in CAD provide a unique opportunity to develop a classification with great clinical applicability. Hence, we will provide a timely new tool for neuroradiologists, clinicians and researchers to facilitate TBI diagnosis, thus improving the treatment and rehabilitation of TBI patients. Finally, TAI-MRI will bring the field forward by increasing our understanding of the pathophysiology of TBI, and how reduced consciousness can be linked to injury type and location and outcome.

Researcher(s)

• Promoter: Parizel Paul

Research team(s)

• Molecular Imaging and Radiology (MIRA)
• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Small animal positron emission tomography (PET) imaging is an indispensible tool for basic research, drug discovery and development. However, in contrast to clinical scanning, animals need to be immobilized during the scan using anesthetics. Unfortunately, in neuroscience experiments, these anesthetics can alter and obscure the outcome of the PET study. Therefore, we are developing techniques to enable PET scanning of awake and unrestrained rats. The technique will measure the position and motion of the rat's head during the PET scan so that a PET image can be formed as if the rat did not move. We will develop minimally and non-invasive techniques to measure this motion. Compared to the current invasive method that uses a large checkerboard marker these methods have many advantages: it does not introduce animal stress, is less prone to errors due to skin motion and can be used in scanners with small scanner bores. These novelties will boost the practicality and relevance of awake rat brain PET. Secondly, we will develop motion adaptive correction methods that will improve the resolution of the PET images. By doing so the image quality of the motion corrected image will have a resolution that is comparable to the resolution that can be obtained from a scan without motion. Finally, we will extend our method to measure head motion of two rats simultaneously while being scanned. This will, for the first time, let us investigate live animal interaction with PET imaging.

Researcher(s)

• Promoter: Verhaeghe Jeroen

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Small animal positron emission tomography (PET) imaging is an indispensible tool for basic research, drug discovery and development. However, in contrast to clinical scanning, animals need to be immobilized during the scan using anesthetics. Unfortunately, in neuroscience experiments, these anesthetics can alter and obscure the outcome of the PET study. Therefore, we are developing techniques to enable PET scanning of awake and unrestrained rats. The technique will measure the position and motion of the rat's head during the PET scan so that a PET image can be formed as if the rat did not move. We will develop minimally and non-invasive techniques to measure this motion. One method is based on miniscule radioactive point sources that are pasted on the animal's head; the other makes use of a 3D optical camera. These novelties will boost the practicality and relevance of awake rat brain PET. Compared to the current invasive method that uses a large checkerboard marker these methods have many advantages: it does not introduce animal stress, is less prone to errors due to skin motion and can be used in scanners with small scanner bores. A full- scale small animal experiment visualizing the brain response to amphetamine will demonstrate the practicality of the method and show the impact of awake versus anesthetized scanning. The new tracking techniques and the in vivo validation will finally establish awake and unrestrained small animal PET imaging as a valid imaging protocol.

Researcher(s)

• Promoter: Verhaeghe Jeroen

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Tears of the anterior cruciate ligament (ACL) of the knee are a frequent injury with increasing incidence. Surgical treatment of ACL injuries is superior to conservative treatment for the majority of patients to facilitate a return to the desired daily activities, including sports. Although ACL reconstruction using autograft tissue remains the gold standard for treating ACL injuries, there is a current surgical trend toward primary repair of the ACL. Successful surgery requires that the ACL graft or repair tissue transforms into ACL-like tissue. A common challenge in ACL surgery and rehabilitation is the lack of a noninvasive, sensitive outcome measure to evaluate the efficacy of surgical treatment. With the recent developments in MR technology, several advanced imaging techniques have now become available for use on clinical 3T scanners. In this project we will focus on the use of quantitative diffusion tensor imaging (DTI) to asses the normal, the injured and postoperative ACL. We will conduct a large-scale study to investigate the ability of DTI to monitor ACL healing both in patients with ACL reconstruction and primary repair of the ACL. It is our aim to document within-patient temporal changes using the DTI technique and to correlate DTI metrics with ACL structural properties. This will help in understanding the ACL healing process, and ultimately, in determining the appropriate timing for patients to return to sports.

Researcher(s)

• Promoter: Parizel Paul
• Promoter: Van Dyck Pieter
• Fellow: Van Dyck Pieter

Research team(s)

• Molecular Imaging and Radiology (MIRA)
• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

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: Engelborghs Sebastiaan
• Co-promoter: Parizel Paul
• Co-promoter: Sijbers Jan

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
• Fellow: Staelens Steven

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project