A5069522091- Drug Transport and Resistance Mechanisms
- Dementia and Cognitive Impairment Research
- Radiopharmaceutical Chemistry and Applications
- Alzheimer's disease research and treatments
- Medical Imaging Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- Pediatric Hepatobiliary Diseases and Treatments
- Functional Brain Connectivity Studies
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Advanced MRI Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Orthopaedic implants and arthroplasty
- Hearing Impairment and Communication
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Pharmacological Effects and Toxicity Studies
- Influenza Virus Research Studies
- Hip disorders and treatments
- Sarcoidosis and Beryllium Toxicity Research
- Total Knee Arthroplasty Outcomes
- Interpreting and Communication in Healthcare
- Cardiac, Anesthesia and Surgical Outcomes
- Boron Compounds in Chemistry
- Silk-based biomaterials and applications
University College London
2019-2024
UK Dementia Research Institute
2020-2024
National Hospital for Neurology and Neurosurgery
2019-2024
The Royal Free Hospital
2024
University of Dundee
2023
Harrogate and District NHS Foundation Trust
2023
MRC Unit for Lifelong Health and Ageing
2022
King's College London
2022
London School of Hygiene & Tropical Medicine
2022
Imperial College London
2022
To study the acceptor specificity for human ABCG1 (hABCG1)-mediated cholesterol efflux.Cells overexpressing hABCG1 were created in Chinese Hamster Ovary (CHO-K1) cells and characterized terms of lipid composition. expressed these formed homodimers was mostly present intracellularly. Cholesterol efflux from to HDL2 HDL3 increased but not lipid-free apolipoproteins. A range phospholipid containing acceptors apart high-density lipoprotein (HDL) subclasses also efficient mediating...
Imaging of somatostatin receptor expression is an established technique for staging neuroendocrine neoplasia and determining the suitability patients peptide radionuclide therapy. PET/CT using <sup>68</sup>Ga-labeled analogs superior to earlier agents, but rapid physical decay poses logistic regulatory challenges. <sup>64</sup>Cu has attractive characteristics imaging provides a diagnostic partner therapeutic <sup>67</sup>Cu. Based on promising preclinical studies, we have performed...
The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected biodiverse regions throughout world. Importantly, this national resource available to research community for screening isolation bioactive products. However, despite success in drug discovery, compatibility issues make challenging liquid...
An automated, high-capacity, and high-throughput procedure for the rapid isolation identification of biologically active natural products from a prefractionated library is presented. The semipreparative HPLC method uses 1 mg primary hit fraction produces 22 subfractions in an assay-ready format. Following screening, all fractions are analyzed by NMR, LCMS, FTIR, principle structural classes elucidated. In proof-of-concept study, we show processes involved generating subfractions, throughput...
Peptide receptor radionuclide therapy (PRRT) using radiolabeled octreotate is an effective treatment for somatostatin 2–expressing neuroendocrine tumors. The diagnostic and therapeutic potential of <sup>64</sup>Cu <sup>67</sup>Cu, respectively, offers the possibility a single receptor–targeted peptide conjugate as theranostic agent. A sarcophagine cage amine ligand, MeCOSar (5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid), conjugated to...
Abstract INTRODUCTION We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on fully automated Lumipulse platform with pre‐symptomatic Alzheimer's disease (AD) pathology positron emission tomography (PET). METHODS In 72 individuals from Insight 46 study, CSF Aβ40, Aβ42, total (t‐tau), phosphorylated at site 181 (p‐tau181) were using Lumipulse, INNOTEST, Meso Scale Discovery (MSD) assays inter‐platform Pearson correlations derived. Aβ42 measures adjusted...
The gastrin-releasing peptide receptor (GRPR) is a promising molecular target for imaging and therapy of prostate cancer using bombesin peptides that bind to the with high affinity. Targeted copper theranostics (TCTs) radionuclides, 64Cu 67Cu therapy, offer significant advantages in development next-generation theranostics. [64Cu]Cu-SAR-BBN clinical PET GRPR-expressing cancers. This study explores therapeutic efficacy [67Cu]Cu-SAR-BBN pre-clinical mouse model. was radiolabeled 67Cu, specific...
The goals of this work were to quantify the independent and interactive associations β-amyloid (Aβ) white matter hyperintensity volume (WMHV), a marker presumed cerebrovascular disease (CVD), with rates neurodegeneration examine contributions
A majority of studies investigating the role ligamentum teres (LT) have focused primarily on anatomical and histological descriptions. To date, however, structural properties LT yet to be fully elucidated.To investigate native in a human cadaveric model.Descriptive laboratory study.A total 12 hemipelvises (mean age, 53.6 years; range, 34-63 years) were dissected free all extra-articular soft tissues isolate its acetabular femoral attachments. dynamic tensile testing machine distracted each...
Our aim was to report the use of <sup>64</sup>Cu and <sup>67</sup>Cu as a theranostic pair radionuclides in human subjects. An additional measure whole-organ dosimetry attached somatostatin analog octreotate using sarcophagine MeCOSar chelator (SARTATE) subjects with receptor–expressing lesions confined cranium, thereby permitting normal-organ for remainder body. <b>Methods:</b> Pretreatment PET imaging studies were performed up 24 h after injection [<sup>64</sup>Cu]Cu-SARTATE, estimated...
Abstract Introduction In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. Methods We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals young onset AD. Diffusion tensor measured mean diffusivity (MD). Amyloid beta positron emission tomography were acquired associations microstructural measures assessed. Results When regional volume was adjusted...
The aim of this study was to determine the role N-linked glycosylation in protein stability, intracellular trafficking, and bile acid transport activity salt export pump [Bsep (ATP-binding cassette B11)]. Rat Bsep fused with yellow fluorescent protein, following mutants, which Asn residues putative sites (Asn(109), Asn(116), Asn(122), Asn(125)) were sequentially replaced Gln, constructed by site-directed mutagenesis: single N109Q, double N109Q + N116Q, triple N116Q N122Q, quadruple N122Q...
The human canalicular multispecific organic anion transporter (cMOAT), known as the multidrug resistance-associated protein 2 (MRP2), is normally expressed in liver and to a lesser extent kidney proximal tubules. In these tissues MRP2 specifically localizes apical membrane. construction of fused green fluorescent protein, subsequent site-directed mutagenesis enabled identification targeting signal that responsible for its localization polarized cells. specific due C-terminal tail not present...
Radionuclide therapy targeting prostate-specific membrane antigen (PSMA) is promising for prostate cancer. We previously reported a ligand, <sup>64</sup>Cu-CuSarbisPSMA, featuring 2 lysine-ureido-glutamate groups. Here, we report the therapeutic potential of <sup>67</sup>Cu-CuSarbisPSMA. <b>Methods:</b> Growth PSMA-positive xenografts was evaluated after treatment with <sup>67</sup>Cu-CuSarbisPSMA or <sup>177</sup>Lu-LuPSMA imaging and (I&T). <b>Results:</b> At 13 d injection, tumor...
Abstract INTRODUCTION The Centiloid scale aims to harmonize amyloid beta (Aβ) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized (CT) data and are influenced by scanner differences, we investigated the transformation with from Insight 46 acquired PET/magnetic resonanceimaging (MRI). METHODS We transformed standardized uptake value ratios (SUVRs) 432 florbetapir PET/MRI scans processed whole cerebellum (WC) white...
Background Consistent patterns of reduced cortical thickness have been identified in early Alzheimer’s disease (AD). However, the pathological factors that influence rates thinning within these AD signature regions remain unclear. Methods Participants were from Insight 46 substudy MRC National Survey Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations baseline cerebral β-amyloid (Aβ) deposition,...
Abstract Background A major challenge to the long-term success of neuroblastoma therapy is widespread metastases that survive initial as minimal residual disease (MRD). The SSTR2 receptor expressed by most tumors making it an attractive target for molecularly targeted radionuclide therapy. SARTATE consists octreotate, which targets receptor, conjugated MeCOSar, a bifunctional chelator with high affinity copper. Cu-SARTATE offers potential both detect and treat MRD using [ 64 Cu]Cu-SARTATE...
Introduction We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology positron emission tomography (PET). Methods In 72 individuals from Insight 46 study, CSF Aβ40, Aβ42, total (t-tau), phosphorylated at site 181 (p-tau181) were using Lumipulse, INNOTEST, Meso Scale Discovery (MSD) assays, inter-platform Pearson correlations derived. Logistic regressions...
Abstract Background: Mutations in the human familial intrahepatic cholestasis gene, FIC1 , result progressive type 1 children and benign recurrent cholestasis. The present study was performed to determine whether transports bile acids and/or influences activity of apical acid transporters. Methods: secretion assay utilized transfected Madin–Darby canine kidney (MDCK) cells, which stably express uptake protein, Na+/taurocholate co‐transporting polypeptide (NTCP). These cells were then...
A 53 year-old African American woman with a three-year history of pulmonary sarcoidosis had follow-up computed tomographic scan to evaluate the status her disease and response treatment. On scan, an abnormal, hypodense mass on left renal superior pole, which was not present previous scans, incidentally discovered. The initial concern carcinoma, despite lack any urinary symptoms. She underwent further evaluation magnetic resonance, enhancement pattern shape were more suggestive lymphoma or...