A5050310576- Radiopharmaceutical Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Click Chemistry and Applications
- Medical Imaging Techniques and Applications
- Thyroid Cancer Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Advanced MRI Techniques and Applications
- Lanthanide and Transition Metal Complexes
- Extracellular vesicles in disease
- Monoclonal and Polyclonal Antibodies Research
- MRI in cancer diagnosis
- S100 Proteins and Annexins
- Peptidase Inhibition and Analysis
- Prostate Cancer Treatment and Research
- Cancer Research and Treatments
- Nanoparticle-Based Drug Delivery
- Lung Cancer Treatments and Mutations
- Cancer, Lipids, and Metabolism
- Trace Elements in Health
- Drug Transport and Resistance Mechanisms
- Ultrasound and Hyperthermia Applications
- Radiation Therapy and Dosimetry
- Glutathione Transferases and Polymorphisms
- Mesenchymal stem cell research
King's College London
2020-2024
St Thomas' Hospital
2020-2024
Aalborg University
2022
Beaumont Hospital
2022
Norwegian University of Science and Technology
2016-2020
St Olav's University Hospital
2017-2019
The majority of cancer patients with advanced disease experience weight loss, including loss lean body mass. Severe is characteristic for cachexia, a condition that significantly impairs functional status and survival. underlying causes cachexia are incompletely understood, currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction cytosolic constituents systemically induced by starvation. We hypothesized starvation-mimicking signaling...
Glutaminase inhibitors target cancer cells by blocking the conversion of glutamine to glutamate, thereby potentially interfering with anaplerosis and synthesis amino acids glutathione. The drug CB-839 has shown promising effects in preclinical experiments is currently undergoing clinical trials several human malignancies, including triple-negative breast (TNBC). However, response glutaminase variable there a need for identification predictive biomarkers. aim this study was determine how...
Exosomes or small extracellular vesicles (sEVs) are increasingly gaining attention for their potential as drug delivery systems and biomarkers of disease. Therefore, it is important to understand in vivo biodistribution using imaging techniques that allow tracking over time at the whole-body level. Positron emission tomography (PET) allows short- long-term radiolabeled compounds both animals humans with excellent quantification properties compared other nuclear techniques. In this report, we...
Abstract Positron emission particle tracking (PEPT) enables 3D localization and of single positron-emitting radiolabelled particles with high spatiotemporal resolution. The translation PEPT to the biomedical imaging field has been limited due lack methods radiolabel biocompatible sufficient specific activity protocols isolate a in sub-micrometre size range, below threshold for capillary embolization. Here we report two key developments: synthesis 68 Ga-radiolabelling homogeneous silica 950...
Abstract Background The majority of patients with advanced cancer develop cachexia, a weight loss syndrome that severely reduces quality life and limits survival. Our understanding the underlying mechanisms cause condition is limited, there are currently no treatment options can completely reverse cachexia. Several tumour‐derived factors inflammatory mediators have been suggested to contribute in cachectic patients. However, inconsistencies between studies recurrent. Activin A interleukin 6...
// Caroline K. Søgaard 1, 7 , Siver A. Moestue 2, 3, 4 Morten B. Rye Jana Kim 5 Anala Nepal 1 Nina-Beate Liabakk Siri Bachke Tone F. Bathen Marit Otterlei 6, and Deborah Hill Department of Cancer Research Molecular Medicine, Norwegian University Science Technology (NTNU), Trondheim, Norway 2 Circulation Medical Imaging, 3 Laboratory Women's Children's Health, Pharmacy, Faculty Health Sciences, Nord University, Namsos, Radiology, St. Olavs Hospital, Trondheim 6 APIM Therapeutics A/S, Clinic...
A new radiotracer [ 68 Ga]Ga-THP-tetrazine for bioorthogonal click radiochemistry is presented. Its ability pretargeted imaging of long-circulating liposomal nanomedicines was tested in vitro and vivo both healthy tumour murine models.
A novel photoactivatable Pt(IV) diazido anticancer agent, Pt-succ-DFO, bearing a pendant deferoxamine (DFO) siderophore for radiometal chelation, has been synthesized the study of its in vivo behavior with radionuclide imaging. Pt-succ-DFO complexation Fe(III) and Ga(III) ions yielded new heterobimetallic complexes that maintain photoactivation properties photocytotoxicity parent Pt complex human cancer cell lines. Radiolabeled Pt-succ-DFO-68Ga (t1/2 = 68 min, positron emitter) was readily...
Calcium minerals such as hydroxyapatite (HAp) can be detected noninvasively in vivo using nuclear imaging agents [18F]NaF (available from cyclotrons), for positron emission tomography (PET) and 99mTc-radiolabeled bisphosphonates (BP; available 99mTc generators single photon computed (SPECT) or scintigraphy). These two types of allow detection bone metastases (based on the presence HAp) vascular calcification lesions (that contain HAp other calcium minerals). With aim developing a...
Amino acid utilization is perturbed in cancer cells, which rewire their metabolism to support cell survival and proliferation.This metabolic reprogramming can be exploited for diagnostic purposes through positron emission tomography imaging of fluorine-18 labeled amino acids.Despite its promise, little known regarding transporter-recognition non-natural stereoisomers or utility imaging.We report here the synthesis vivo characterization a radiolabeled (R)-4-(3-18 F-fluoropropyl)-ʟ-glutamate...
Positron Emission Tomography (PET) imaging with antibody-based contrast agents frequently uses the radioisotopes [64Cu]Cu2+ and [89Zr]Zr4+. The macrobicyclic chelator commonly known as sarcophagine (sar) is ideal for labeling receptor-targeted biomolecules [64Cu]Cu2+. siderophore chelator, desferrioxamine-B (dfo), has been widely used to incorporate [89Zr]Zr4+ into antibodies. Here, we describe new bifunctional chelators of sar dfo: these have functionalized dibromomaleimides (dbm), that...
Abstract Purpose: Patients with aggressive thyroid cancer are frequently failed by the central therapy of ablative radioiodide (RAI) uptake, due to reduced plasma membrane (PM) localization sodium/iodide symporter (NIS). We aimed understand how NIS is endocytosed away from PM human cells, and whether this was druggable in vivo. Experimental Design: Informed analysis endocytic gene expression patients cancer, we used mutagenesis, NanoBiT interaction assays, cell surface biotinylation RAI...
To compare the effects of two anti-angiogenic drugs, bevacizumab and a cytosolic phospholipase A2-α inhibitor (AVX235), on relationship between vascular structure dynamic contrast enhanced (DCE)-MRI measurements in patient-derived breast cancer xenograft model.Mice bearing MAS98.12 tumors were randomized into three groups: bevacizumab-treated (n = 9), AVX235-treated control 8). DCE-MRI was performed pre- post-treatment. Median initial area under concentration-time curve (IAUC60 ) volume...
Pretargeted PET imaging using bioorthogonal chemistry is a leading strategy for the tracking of long-circulating agents such as antibodies and nanoparticle-drug delivery systems with short-lived isotopes. Here, we report synthesis, characterisation in vitro/vivo evaluation new 68Ga-based radiotracer [68Ga]Ga-THP-Tetrazine ([68Ga]Ga-THP-Tz) click radiochemistry vivo labelling slow pharmacokinetics. THP-tetrazine (THP-Tz) can be radiolabelled to give [68/67Ga]Ga-THP-Tz at room temperature less...
Despite a rise in clinical use of radiopharmaceutical therapies, the biological effects radionuclides and their relationship with absorbed radiation dose are poorly understood. Here, we set out to define this for Auger electron emitters [
Background Steady state susceptibility contrast (SSC)‐MRI provides information on vascular morphology but is a rarely used method. Purpose To investigate the utility of ultrasmall superparamagnetic iron oxide particles (USPIOs) GEH121333 for measuring tumor response to bevacizumab and compare this with gadolinium‐based DCE‐MRI. Study Type Prospective preclinical animal model study. ANIMAL MODEL Mice bearing subcutaneous TOV‐21G human ovarian cancer xenografts treated (n = 9) or saline 9)....
The coxsackie and adenovirus receptor (CAR) is a member of the junctional adhesion molecule (JAM) family receptors localised to epithelial cell tight adherens junctions. CAR has been shown be highly expressed in lung cancer where it proposed promote tumor growth regulate mesenchymal transition (EMT), however potential role metastasis remains poorly understood. To better understand this progression, we manipulated expression both epithelial-like mesenchymal-like cells. In cases,...
Auger electron therapy exploits the cytotoxicity of low-energy electrons emitted during radioactive decay that travel very short distances (typically <1 μm). 201Tl, with a half-life 73 h, emits ∼37 and other secondary per can be tracked in vivo as its gamma emissions enable SPECT imaging. Despite useful nuclear properties satisfactory bifunctional chelators to incorporate it into bioconjugates for molecular targeting have not been developed. H4pypa, H5decapa, H4neunpa-NH2, H4noneunpa are...
Non-invasive imaging techniques to dynamically map whole-body trafficking of essential metals in vivo health and diseases are needed. Despite 62Zn having appropriate physical properties for positron emission tomography (PET) (half-life, 9.3 h; emission, 8.2%), its complex decay via 62Cu 10 min; 97%) has limited use. We aimed develop a method extract from 62Zn/62Cu generator, investigate use zinc despite decay. prepared by proton irradiation natural copper foil was used construct conventional...
Ultrasound (US) in combination with microbubbles (MB) has had promising results improving delivery of chemotherapeutic agents. However, most studies are done immunodeficient mice xenografted tumors. We used two phenotypes the spontaneous transgenic adenocarcinoma mouse prostate (TRAMP) model to evaluate if US + MB could enhance therapeutic efficacy cabazitaxel (Cab). Cab was either injected intravenously as free drug or encapsulated into nanoparticles. In both cases, transiently reduced...
Background: Multi-tracer PET/SPECT imaging enables different modality tracers to be present simultaneously, allowing multiple physiological processes imaged in the same subject, within a short time-frame. Fluorine-18 and technetium-99m, two commonly used PET SPECT radionuclides respectively, possess emission profiles, offering potential for one presence of other. However, impact each radionuclide on scanning other could significant lead confounding results. Here we use combinations 18F 99mTc...
A sufficient dietary intake of the vitamin niacin is essential for normal cellular function. Niacin transported into cells by monocarboxylate transporters: sodium-dependent transporter (SMCT1 and SMCT2) (MCT1). Despite importance in biological systems, surprisingly, its vivo biodistribution trafficking living organisms has not been reported. The availability radiolabelled with short-lived positron emitting radionuclide carbon-11 ([11C]niacin) would enable quantitative study this endogenous...
Introduction Common variants in the SLC30A8 gene, encoding secretory granule zinc transporter ZnT8 (expressed largely pancreatic islet alpha and beta cells), are associated with altered risk of type 2 diabetes. Unexpectedly, rare loss-of-function (LoF) described heterozygous individuals only, protective against disease, even though knockout homologous gene mice leads to unchanged or impaired glucose tolerance. Here, we aimed determine how one two copies mutant R138X allele mouse impacts...
Abstract Background The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a widely used genetically engineered spontaneous cancer model. However, both degree malignancy and time onset vary. While most mice display slowly progressing cancer, subgroup develops fast‐growing poorly differentiated (PD) tumors, making model challenging to use. We investigated feasibility using ultrasound (US) imaging screen for PD tumors compared performances US magnetic resonance (MRI) in providing...