A5002460930- Adenosine and Purinergic Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Click Chemistry and Applications
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Brain Metastases and Treatment
- Neuropeptides and Animal Physiology
- Parkinson's Disease Mechanisms and Treatments
- Multiple Sclerosis Research Studies
- Tryptophan and brain disorders
- Mast cells and histamine
- Neurological disorders and treatments
- Neurological Complications and Syndromes
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Medical Imaging Techniques and Applications
- Radiopharmaceutical Chemistry and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Chemokine receptors and signaling
- Estrogen and related hormone effects
- Immune Cell Function and Interaction
- Retinoids in leukemia and cellular processes
- Eicosanoids and Hypertension Pharmacology
- Nuclear Receptors and Signaling
- Fluorine in Organic Chemistry
University of Pennsylvania
2018-2023
Vrije Universiteit Amsterdam
2021
Amsterdam University Medical Centers
2019-2021
Amsterdam Neuroscience
2016-2021
California University of Pennsylvania
2020
Philadelphia University
2020
Amsterdam UMC Location Vrije Universiteit Amsterdam
2013-2017
The University of Sydney
2017
Johnson & Johnson (Brazil)
2002
Microglia are major players in the pathogenesis of multiple sclerosis (MS) and may play a dual role disease progression. The activation status microglia vivo is highly dynamic occurs as continuum, with pro-inflammatory anti-inflammatory phenotypes on either end this spectrum. Little known about dynamics MS due to lack diagnostic tools. Positron emission tomography (PET) imaging powerful non-invasive technique that allows real-time central nervous system, depending availability selective PET...
Neuroinflammation, in particular activation of microglia, is thought to play an important role the progression neurodegenerative diseases. In activated purinergic P2X 7 receptor upregulated. A‐740003, a highly affine and selective antagonist, promising candidate for development radiotracer imaging neuroinflammation by positron emission tomography. For this purpose, [ 11 C]A‐740003 was synthesised evaluated vivo with respect both tracer metabolism biodistribution. plasma, moderate metabolic...
Abstract The P2X 7 receptor plays a significant role in microglial activation, and as potential drug target, the is also an interesting target positron emission tomography. current study aimed at development evaluation of potent tracer targeting receptor, to which end four adamantanyl benzamide analogues with high affinity for human were labelled carbon-11. All could be obtained excellent radiochemical yield purity molar activity, all entered rat brain. [ 11 C]SMW139 showed highest metabolic...
Abstract Purpose The novel PET tracer [ 11 C]SMW139 binds with high affinity to the P2X 7 receptor, which is expressed on pro-inflammatory microglia. purposes of this first in-man study were characterise pharmacokinetics in patients active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) evaluate its potential identify vivo neuroinflammation RRMS. Methods Five RRMS 5 age-matched HC underwent 90-min dynamic scans, online continuous manual arterial sampling generate a...
Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess efficacy of therapies aimed reduce tissue damaging activities microglia and/or promote protective these cells, suitable pre-clinical clinical tools vivo analysis dynamics required. The aim this work was identify new translational markers anti-inflammatory / state development novel PET tracers. Methods: New...
All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer differentiation. However, the clinical use all-trans-retinoic in treatment cancer significantly hampered by its toxicity prompt emergence resistance, believed to be caused increased metabolism. Inhibitors metabolism may therefore prove valuable cancer. In this study, we characterize R116010 as new anticancer drug that vitro, potently inhibits intact T47D cells with an IC50-value 8.7 nM. addition, selective...
Adamantanyl benzamide 1 was identified as a potent P2X7R antagonist but failed to progress further due poor metabolic stability. We describe the synthesis and SAR of series bioisosteres explore improvements in pharmacological properties this lead. Initial efforts investigated heteroaromatic bioisosteres, which demonstrated improved physicochemical reduced antagonism. Installation bioisosteric fluorine on adamantane bridgeheads well tolerated led with Trifluorinated 34 optimal parameters,...
Ultra-high throughput <italic>in silico</italic> screening identified molecules that bind to α-synuclein fibrils, which were analyzed by photo-crosslinking, structure-activity studies, and radioligand binding validate this approach for finding imaging probes.
Fluorescent molecules are powerful tools for imaging α-synuclein pathology. Here, we demonstrate that benzofuranone derivatives have high affinity and display different binding to α-synucleinopathies in post-mortem brain tissue.
The P2Y12 receptor (P2Y12R) is uniquely expressed on microglia in the brain, and its expression level directly depends microglial activation state. Therefore, P2Y12R provides a promising imaging marker for distinguishing pro- anti-inflammatory phenotypes, both of which play crucial roles neuroinflammatory diseases. In this study, three antagonists were selected from literature, radiolabeled with carbon-11 or fluorine-18, evaluated healthy Wistar rats. Brain was performed without blocking...
Abstract Background Non-invasive imaging of the activation status microglia and ability to identify a pro- or anti-inflammatory environment can provide valuable insights not only into pathogenesis neuro-inflammatory neurodegenerative diseases but also monitoring efficacy immunomodulatory therapies. P2X 7 R is highly expressed on pro-inflammatory [ 11 C]SMW139, specific tracer for positron emission tomography imaging, showed good pharmacokinetics, stability, brain permeability in vivo. Our...