A5009219071- Radiopharmaceutical Chemistry and Applications
- Lanthanide and Transition Metal Complexes
- Medical Imaging Techniques and Applications
- PARP inhibition in cancer therapy
- Metal complexes synthesis and properties
- Cancer, Hypoxia, and Metabolism
- Chemical Reactions and Isotopes
- Magnetism in coordination complexes
- Fluorine in Organic Chemistry
- DNA Repair Mechanisms
- Atomic and Subatomic Physics Research
- Advanced MRI Techniques and Applications
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Radiation Therapy and Dosimetry
- S100 Proteins and Annexins
- Organometallic Compounds Synthesis and Characterization
- Cell death mechanisms and regulation
- Click Chemistry and Applications
- Immune Response and Inflammation
- Epilepsy research and treatment
- Radioactive element chemistry and processing
- Metalloenzymes and iron-sulfur proteins
- Trace Elements in Health
- Acute Myocardial Infarction Research
University of Oxford
2008-2022
CRUK/MRC Oxford Institute for Radiation Oncology
2008-2022
University Hospital of Wales
2022
Cardiff University
2021-2022
Churchill Hospital
2020
King's College London
2013-2017
Oxfam
2014-2015
Oxford Research Group
2014
St Thomas' Hospital
2013-2014
University of Surrey
2013
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in target tissue metastasis -the premetastatic niche.As crucial players pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression.We report application antibody-based single-photon emission computed tomography (SPECT) for detection S100A8/A9 vivo as imaging marker priming.Methods A...
Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, single agents, or a part of combination therapies. Imaging PARP using radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging novel PARP-targeting agents. <b>Methods:</b> Here, via the copper-mediated <sup>18</sup>F-radiofluorination aryl boronic esters, we accessed, first time (to our...
<sup>64</sup>Cu-diacetyl-bis(<i>N</i><sup>4</sup>-methylthiosemicarbazonate), <sup>64</sup>Cu-ATSM, continues to be investigated clinically as a PET agent both for delineation of tumor hypoxia and an effective indicator patient prognosis, but there are still aspects the mechanism action that not fully understood. <b>Methods:</b> The retention radioactivity in tumors after administration <sup>64</sup>Cu-ATSM vivo is substantially higher with significant hypoxic fraction. This...
A range of new carboxylate functionalised bis(thiosemicarbazone) ligands and their Cu(II) complexes have been prepared, fully characterised radiolabeled in high yield with both 64Cu 99mTc. Conjugation to a bombesin derivative was achieved using standard solid phase synthetic methodologies the 64Cu-labeled conjugate shown good tumour uptake mice xenografted PC-3 tumours.
A water-soluble glucose conjugate of the hypoxia tracer <sup>64</sup>Cu-diacetyl-bis(<i>N</i><sup>4</sup>-methylthiosemicarbazone) (<sup>64</sup>Cu-ATSM) was synthesized and radiolabeled (<sup>64</sup>Cu-ATSE/A-G). Here we report our initial biological experiments with <sup>64</sup>Cu-ATSE/A-G compare results those obtained for <sup>64</sup>Cu-ATSM <sup>18</sup>F-FDG. <b>Methods:</b> The uptake into HeLa cells in vitro investigated at a range dissolved oxygen concentrations representing...
Background Preclinical imaging requires anaesthesia to reduce motion-related artefacts. For direct translational relevance, must not significantly alter experimental outcome. This study reports on the effects of both anaesthetic and carrier gas upon uptake [64Cu]-CuATSM, [99mTc]-HL91 [18F]-FMISO in a preclinical model tumor hypoxia. Methodology/Principal Findings The effect was studied 6 groups CaNT-bearing CBA mice using or [18F]-FMISO. Mice were anaesthetised with isoflurane air, pure...
Pyrene-appended ytterbium complexes have been prepared using Ugi reactions to vary the chromophore-lanthanide separation. Formation of ytterbium(iii) excited state is sensitised via both singlet and triplet states chromophore. Energy transfer from latter relatively slow, gives rise oxygen-dependent luminescence.
Oxygen dependent luminescence in pyrene appended europium complexes is shown to arise two different ways. The nature of the pathway can be controlled by varying lanthanide–pyrene separation.
Flumazenil (FMZ) is a functionally silent imidazobenzodiazepine which binds to the benzodiazepine binding site of approximately 75% brain γ-aminobutyric acid-A receptors (GABAARs). Positron Emission Tomography (PET) imaging GABAARs with [11C]FMZ has been used evidence alterations in neuronal density, assess target engagement novel pharmacological agents, and study disorders such as epilepsy Huntington's disease. Despite potential FMZ PET short half-life (t1/2) carbon-11 (20 min) limited more...
Abstract The synthesis of zinc(II) and copper(II) complexes an unsymmetrical bis(thiosemicarbazonato) ligand containing a reactive styrene group are reported. compounds have been characterised by range techniques including reverse‐phase HPLC, cyclic voltammetry, NMR, UV/Vis, electron paramagnetic resonance fluorescence emission spectroscopy. Time‐dependent density functional theory calculations used to assign the electronic absorption spectrum [Zn II ATSM] probe nature fluorescent excited...
Copper(ii)bis(thiosemicarbazonato) complexes such as [64Cu]Cu-ATSM continue to be investigated for positron emission tomography (PET) imaging of tumour hypoxia. However, the currently proposed mechanisms mode action these are unable account fully their observed biological behaviour. In order examine roles copper metal and ligand, we designed a pair 123I/64Cu-copper bis(thiosemicarbazonates), radiolabelled at either or ligand. vitro cellular retention studies orthogonal demonstrate first time...
Abstract Purpose Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous normal tissue. Hence, the injected mass, molar activity potential pharmacological effects important considerations use of radiolabelled inhibitors diagnostic radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying [ 18 F]olaparib mass Total to investigate on...
Poly (ADP-ribose) polymerase (PARP) inhibitors are extensively studied and used as anti-cancer drugs, single agents or in combination with other therapies. Most radiotracers developed to date have been chosen on the basis of strong PARP1-3 affinity. Herein, we propose study AZD2461, a PARP inhibitor lower affinity towards PARP3, investigate its potential for targeting vivo.
The synthesis of three pairs orthogonally labelled fluorinated Cu bis(thiosemicarbazonato) complexes is presented. These are the first examples (18)F-labelled Cu(II)-complexes designed to serve as new hypoxia selective PET tracers and mechanistic probes study mode action this class markers. In vitro evaluation revealed that Cu-complex derived from amide coupling suitable for in vivo work.
Meeting Summary The 21st annual symposium of the International Isotope Society's United Kingdom Group took place at Møller Centre, Churchill College, Cambridge, UK, on Friday 12th October 2012. meeting was attended by around 60 delegates from academia and industry, life sciences, chemical, radiochemical scientific instrument suppliers. Delegates were welcomed Dr Ken Lawrie (GlaxoSmithKline, chair IIS UK group). subsequent programme consisted oral poster presentations isotopic chemistry...
Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for treatment cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in move towards more personalised medicine. The aim this study was synthesise investigate first 18F-labelled inhibitor [18F]1 non-invasive imaging protein pharmacokinetics. Radiofluorination confirmed selective (1)...