- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- MRI in cancer diagnosis
- Radiomics and Machine Learning in Medical Imaging
- Advanced MRI Techniques and Applications
- Neuroendocrine Tumor Research Advances
- Prostate Cancer Treatment and Research
- Nanoplatforms for cancer theranostics
- Mesenchymal stem cell research
- Neuroblastoma Research and Treatments
- Nanoparticle-Based Drug Delivery
- Peptidase Inhibition and Analysis
- Osteoarthritis Treatment and Mechanisms
- Glioma Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Medical Imaging and Pathology Studies
- Cancer Research and Treatments
- Diabetic Foot Ulcer Assessment and Management
- Lung Cancer Research Studies
- Xenotransplantation and immune response
- Ultrasound and Hyperthermia Applications
- Neuropeptides and Animal Physiology
- Photoacoustic and Ultrasonic Imaging
- Computational Drug Discovery Methods
- Cell Image Analysis Techniques
Erasmus MC Cancer Institute
2024
Erasmus MC
2015-2024
Erasmus University Rotterdam
2012-2021
Abstract Purpose Various radiolabeled prostate-specific membrane antigen (PSMA)–targeting tracers are clinically applied for prostate cancer (PCa) imaging and targeted radionuclide therapy. The PSMA binding affinities, biodistribution, DNA-damaging capacities of these radiotracers have not yet been compared in detail. A major concern PSMA-targeting is the toxicity other PSMA-expressing organs, such as salivary glands, thus demanding careful evaluation most optimal safest radiotracer. In this...
Glioblastoma multiforme (GBM) has a mean survival of only 15 months. Tumour heterogeneity and blood-brain barrier (BBB) mainly hinder the transport active agents, leading to late diagnosis, ineffective therapy inaccurate follow-up. The use hydrogel nanoparticles, particularly hyaluronic acid as naturally occurring polymer extracellular matrix (ECM), great potential in improving drug molecules and, furthermore, facilitatating early diagnosis by effect hydrodenticity enabling T1 boosting...
Abstract Mesenchymal stem cells (MSC) are promising candidates for use as a biological therapeutic. Since locally injected MSC disappear within few weeks, we hypothesize that efficacy of can be enhanced by prolonging their presence. Previously, encapsulation in alginate was suggested suitable approach this purpose. We found no differences between the two types, high mannuronic acid (High M) and guluronic G), regarding viability, immunomodulatory capability, or retention capsule integrity...
Patients with neuroendocrine tumors (NETs) can be treated peptide receptor radionuclide therapy (PRRT). Here, the somatostatin analogue octreotate radiolabeled lutetium-177 is targeted to NET cells by binding subtype 2 (SST2). During radioactive decay, DNA damage induced, leading cell death. Although proves effective, mortality rates remain high. To appropriately select more optimal treatment strategies, it essential first better understand radiobiological responses of tumor PRRT. Methods:...
Background Magnetic resonance imaging (MRI), together with histology, is widely used to diagnose and monitor treatment in oncology. Spatial correspondence between these modalities provides information about the ability of MRI characterize cancerous tissue. However, registration complicated by deformations during pathological processing, differences scale content. Methodology/Principal Findings This study proposes a methodology for establishing an accurate 3D relation histological sections...
Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types lower SSTR expression, including breast (BC). To date, two reported higher binding of the antagonist than agonist BC, but both a number cases were evaluated. In this preclinical study, we further investigated whether...
Tumor-associated macrophages (TAMs) promote cancer growth and metastasis, but their role in tumor development needs to be fully understood due the dynamic changes of microenvironment (TME). Here, we report an approach visualize TAMs by optical imaging Fluorine-19 ( 19 F) magnetic resonance (MRI) that is largely applied track immune cells vivo . are targeted with PLGA-PEG-mannose nanoparticles (NPs) encapsulating perfluoro-15-crown-5-ether (PFCE) as MRI contrast agent. These particles...
Although efficient delivery and distribution of treatment agents over the whole tumor is essential for successful treatment, most these cannot be visualized. However, with single-photon emission computed tomography (SPECT), both uptake radiolabeled peptides can visualized in a neuroendocrine model overexpressing somatostatin receptors. A heterogeneous peptide often observed tumors. We hypothesized that spatially related to perfusion, vessel density permeability, as imaged quantified by...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by thymidine phosphorylase (TP) deficiency resulting in systemic accumulation of (d-Thd) and deoxyuridine (d-Urd) characterized early-onset neurological gastrointestinal symptoms. Long-term effective safe treatment not available. Allogeneic bone marrow transplantation may improve clinical manifestations but carries disease transplant-related risks. In this study, lentiviral vector-based...
Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate (177Lu-TATE) treatment, also referred to as peptide radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI SPECT/CT, we studied tumour characteristics therapeutic responses after different (combined) administration schemes a murine model order...
Abstract Purpose Radiolabeled NeoB is a promising gastrin-releasing peptide receptor (GRPR)–targeting radiopharmaceutical for theranostics of GRPR-expressing malignancies, e.g. , prostate cancer (PCa). The aim this study was to evaluate the effect different doses [ 177 Lu]Lu-NeoB on balance between therapeutic efficacy and safety in preclinical PCa model. Procedures To determine Lu]Lu-NeoB, PC-3 xenografted mice received 3 sham injections (control group) or 30 MBq/300 pmol, 40 MBq/400 60...
Nuclear and optical dual-modality probes can be of great assistance in prostate cancer localization, providing the means for both preoperative nuclear imaging intraoperative surgical guidance. We developed a series based on backbone established GRPR-targeting radiotracer NeoB. The inverse electron demand Diels–Alder reaction was used to integrate sulfo-cyanine 5 dye. Indium-111 radiolabeling, stability studies competition binding assay were carried out. Pilot biodistribution performed PC-3...
Background: Glioblastoma is an aggressive and incurable type of brain cancer. Little progress has been made in the development effective new therapies past decades. The blood–brain barrier (BBB) drug efflux pumps, which together hamper delivery to these tumors, play a pivotal role gap between promising preclinical findings failure clinical trials. Therefore, selecting drugs that can reach tumor region pharmacologically concentrations major importance. Methods: In current study, we utilized...
Spatial correspondence between histology and multi sequence MRI can provide information about the capabilities of non-invasive imaging to characterize cancerous tissue. However, shrinkage deformation occurring during excision tumor histological processing complicate co registration MR images with sections. This work proposes a methodology establish detailed 3D relation sections in vivo data. The key features are very dense sampling (up 100 slices per tumor), mutual based non-rigid B-spline...
Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced proteasome inhibitors bortezomib.In this study, we assessed several combined treatment modalities in vitro vivo. By cell-based functional analyses, 3D ovo an orthotopic mouse model, demonstrated sensitizing effects...
Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted in vivo will be helpful to detect impaired at an early stage allows interventions improve engraftment outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34+ cells, 19F-containing PLGA nanoparticles which were detectable both flow cytometry magnetic...
As model system, a solid-tumor patient-derived xenograft (PDX) characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this model, tumor uptake of targeting peptides expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous distribution the xenografts as assessed vitro autoradiography. We hypothesized that delivery cells is dictated adequate local perfusion....
Abstract Purpose Current clinical measurements for tumor treatment efficiency rely often on changes in volume measured as shrinkage by CT or MRI, which become apparent after multiple lines of and pose a physical psychological burden the patient. Detection therapy-induced cell death can be fast measure efficiency. However, there are no reliable tools detection necrosis. Previously, we studied necrosis avidity cyanine-based fluorescent dyes, suffered long circulation times before could imaged...
Anti‐tumor efficacy of targeted peptide‐receptor radionuclide therapy (PRRT) relies on several factors, including functional tumor vasculature. Little is known about the effect PRRT With dynamic contrast‐enhanced (DCE‐) MRI, vasculature imaged and quantified using contrast agents. In small animals DCE‐MRI a challenging application. We optimized clinical sequence for fast hemodynamic acquisitions, time‐resolved imaging kinetics (TRICKS), to obtain images at both high spatial temporal...
Necrosis only occurs in pathological situations and is directly related to disease severity and, therefore, an important biomarker. Tumor necrosis most solid tumors due improperly functioning blood vessels that cannot keep up with the rapid growth, especially aggressively growing tumors. The amount of per tumor volume often correlated proliferation can be used as a diagnostic tool. Furthermore, efficient therapy against will or indirectly lead necrotic cells, detection increased early marker...
In this work, a superficial hyperthermia applicator was designed to be used in small animal studies. The operates at 2.45 GHz and is compatible with magnetic resonance scanner. A temperature controller interfaced the control rate of change target temperature. Operation robustness were validated through phantom vivo experiments.
Multimodality reporter gene imaging combines the sensitivity, resolution and translational potential of two or more signals. The approach has not been widely adopted by animal community, mainly because its utility in this area is unproven. We developed a new complementation-based system where large component split NanoLuc luciferase (LgBiT) presented on surface cells (TM-LgBiT) interacts with radiotracer consisting high-affinity complementary HiBiT peptide labeled radionuclide. Radiotracer...