A5066132044- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- Adenosine and Purinergic Signaling
- Lung Cancer Treatments and Mutations
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
- Neurogenesis and neuroplasticity mechanisms
- Medical Imaging and Pathology Studies
- Immunotherapy and Immune Responses
- Peripheral Neuropathies and Disorders
- Radiomics and Machine Learning in Medical Imaging
- Tuberculosis Research and Epidemiology
- Protein Tyrosine Phosphatases
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- S100 Proteins and Annexins
- Bone health and treatments
- Multiple Myeloma Research and Treatments
- Cancer Treatment and Pharmacology
- Hereditary Neurological Disorders
- Chemical Synthesis and Analysis
Amsterdam University Medical Centers
2019-2025
Amsterdam Neuroscience
2018-2025
Vrije Universiteit Amsterdam
2020-2025
Amsterdam UMC Location Vrije Universiteit Amsterdam
2017-2024
Cancer Center Amsterdam
2023-2024
Dutch Cancer Society
2023-2024
University of Pittsburgh
2013-2021
Centre National de la Recherche Scientifique
2010-2014
Laboratoire de Neurosciences Cognitives
2014
Université de Strasbourg
2010-2014
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...
Abstract Purpose Almost all radiolabellings of antibodies with 89 Zr currently employ the hexadentate chelator desferrioxamine (DFO). However, DFO can lead to unwanted uptake in bones due instability resulting metal complex. DFO*-NCS and squaramide ester DFO, DFOSq, are novel analogues that gave more stable complexes than pilot experiments. Here, we directly compare these linker-chelator systems identify optimal immuno-PET reagents. Methods Cetuximab, trastuzumab B12 (non-binding control...
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...
Very late antigen-4 (VLA-4; also known as integrin α4β1) is expressed at high levels in aggressive and metastatic melanoma tumors may provide an ideal target for imaging targeted radionuclide therapy (TRT). 177Lu-DOTA-PEG4-LLP2A (177Lu-LLP2A) a TRT that shows affinity VLA-4 uptake B16F10 mouse vivo. Here, we report efficacy studies of 177Lu-LLP2A, alone combined with immune checkpoint inhibitors (ICIs) (anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), tumor-bearing mice. Methods: Tumor cells...
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...
Abstract The choroid plexus (CP) is a key regulator of the central nervous system (CNS) homeostasis through its secretory, immunological and barrier properties. Accumulating evidence suggests that CP plays pivotal role in pathogenesis multiple sclerosis (MS), but underlying mechanisms remain largely elusive. To get comprehensive view on MS, we studied transcriptomic alterations human progressive MS non-neurological disease controls using RNA sequencing. We identified 17 genes with...
Abstract Positron emission tomography and computed imaging (PET/CT) is an increasingly valuable tool for diagnosing tuberculosis (TB). The glucose analog [18F]fluoro-2-deoxy-2-d-glucose ([18F]-FDG) commonly used in PET/CT that retained by metabolically active inflammatory cells granulomas, but lacks specificity particular cell types. A PET probe could identify recruitment differentiation of different populations granulomas would be a useful research improve TB diagnosis treatment. We the...
The recent conditional FDA approval of Aducanumab (Adu) for treating Alzheimer's disease (AD) and the continued discussions around that decision have increased interest in immunotherapy AD other brain diseases. Reliable techniques imaging antibodies may guide decision-making future but needs further development. In this study, we used 89Zr-immuno-PET to evaluate targeting distribution a bispecific brain-shuttle IgG based on Adu with transferrin receptor protein-1 (TfR1) shuttling mechanism,...
Melanoma is a malignant tumor derived from epidermal melanocytes, and it known for its aggressiveness, therapeutic resistance, predisposition late metastasis. Very antigen-4 (VLA-4; also called integrin α<sub>4</sub>β<sub>1</sub>) transmembrane noncovalent heterodimer overexpressed in melanoma tumors that plays an important role growth, angiogenesis, metastasis by promoting adhesion migration of cancer cells. In this study, we evaluated 2 conjugates high-affinity VLA-4 peptidomimetic ligand,...
Malignant melanoma is a highly aggressive cancer, and the incidence of this disease increasing worldwide at an alarming rate. Despite advances in treatment melanoma, patients with metastatic still have poor prognosis low survival New strategies, including targeted radiotherapy, would provide options for who become resistant to therapies such as BRAF inhibitors. Very late antigen-4 (VLA-4) expressed on tumor cells higher levels more may ideal target drug delivery radiotherapy. In study, we...
Very-late-antigen-4 (VLA-4, α<sub>4</sub>β<sub>1</sub> integrin, CD49d/CD29) is a transmembrane adhesion receptor that plays an important role in cancer and immune responses. Enhanced VLA-4 expression has been observed multiple myeloma (MM) cells surrounding stroma. conformational activation associated with MM pathogenesis. promising imaging therapeutic biomarker. <b>Methods:</b> Specificity of <sup>64</sup>Cu-LLP2A (<sup>64</sup>Cu-CB-TE1A1P-PEG<sub>4</sub>-LLP2A), high-affinity...
Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment. However, it is now well-known that PD-1/PD-L1 immunotherapy response inconsistent among patients. The current challenge customize treatment regimens per patient, which could be possible if expression dynamic landscape are known. With positron emission tomography (PET) imaging, image these targets non-invasively system-wide during...
The accelerated approval of the monoclonal antibody (mAb) aducanumab as a treatment option for Alzheimer's Disease and continued discussions about its efficacy have shown that better understanding immunotherapy neurodegenerative diseases is needed. 89Zr-immuno-PET could be suitable tool to open new avenues diagnosis CNS disorders, monitoring disease progression, assessment novel therapeutics.Herein, three different 89 Zr-labeling strategies direct radioiodination with 125 I bispecific...
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 Purpose In the emerging field of antibody treatments for neurodegenerative diseases, reliable tools are needed to evaluate new therapeutics, diagnose and select patients, monitor disease progression, assess therapy response. Immuno-PET combines high affinity exceptional specificity monoclonal antibodies with non-invasive imaging technique positron emission tomography (PET). Its application in brain has been limited due marginal uptake across blood–brain barrier (BBB). The emergence...
Recently,
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...