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Manchester, United Kingdom

Lamare F.,Imperial College London | Hinz R.,Wolfson Molecular Imaging Center | Gaemperli O.,Imperial College London | Pugliese F.,Imperial College London | And 6 more authors.
Journal of Nuclear Medicine | Year: 2011

We investigated whether PET/CT angiography using 11C-(R)- PK11195, a selective ligand for the translocator protein (18 kDa) expressed in activated macrophages, could allow imaging and quantification of arterial wall inflammation in patients with large-vessel vasculitis. Methods: Seven patients with systemic inflammatory disorders (3 symptomatic patients with clinical suspicion of active vasculitis and 4 asymptomatic patients) underwent PET with 11C-(R)-PK11195 and CT angiography to colocalize arterial wall uptake of 11C-(R)-PK11195. Tissue regions of interest were defined in bone marrow, lung parenchyma, wall of the ascending aorta, aortic arch, and descending aorta. Blood-derived and image-derived input functions (IFs) were generated. A reversible 1-tissue compartment with 2 kinetic rate constants and a fractional blood volume term were used to fit the time-activity curves to calculate total volume of distribution (VT). The correlation between VT and standardized uptake values was assessed. Results: V T was significantly higher in symptomatic than in asymptomatic patients using both image-derived total plasma IF (0.55 ± 0.15 vs. 0.27 ± 0.12, P = 0.009) and image-derived parent plasma IF (1.40 ± 0.50 vs. 0.58 ± 0.25, P = 0.018). A good correlation was observed between VT and standardized uptake value (R = 0.79; P = 0.03). Conclusion: 11C-(R)-PK11195 imaging allows visualization of macrophage infiltration in inflamed arterial walls. Tracer uptake can be quantified with image-derived IF without the need for metabolite corrections and evaluated semiquantitatively with standardized uptake values. Copyright © 2011 by the Society of Nuclear Medicine, Inc. Source

Wood S.L.,Wolfson Molecular Imaging Center | Knowles M.A.,Leeds Beckett University | Thompson D.,General Infirmary | Selby P.J.,Leeds Beckett University | Banks R.E.,Leeds Beckett University
Nature Reviews Urology | Year: 2013

Urine is an ideal body fluid for the detection of protein markers produced by urological cancers as it can be sampled noninvasively and contains secreted and directly shed proteins from the prostate, bladder and kidney. Major challenges of working with urine include high inter-individual and intra-individual variability, low protein concentration, the presence of salts and the dynamic range of protein expression. Despite these challenges, significant progress is being made using modern proteomic methods to identify and characterize protein-based markers for urological cancers. The development of robust, easy-to-use clinical tests based on novel biomarkers has the potential to impact upon diagnosis, prognosis and monitoring and could revolutionize the treatment and management of these cancers. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Hammond E.M.,University of Oxford | Asselin M.-C.,Wolfson Molecular Imaging Center | Forster D.,Wolfson Molecular Imaging Center | O'Connor J.P.B.,Institute of Population Health | And 2 more authors.
Clinical Oncology | Year: 2014

Hypoxia was identified as a microenvironmental component of solid tumours over 60 years ago and was immediately recognised as a potential barrier to therapy through the reliance of radiotherapy on oxygen to elicit maximal cytotoxicity. Over the last two decades both clinical and experimental studies have markedly enhanced our understanding of how hypoxia influences cellular behaviour and therapy response. Furthermore, they have confirmed early assumptions that low oxygenation status in tumours is an exploitable target in cancer therapy. Generally such approaches will be more beneficial to patients with hypoxic tumours, necessitating the use of biomarkers that reflect oxygenation status. Tissue biomarkers have shown utility in many studies. Further significant advances have been made in the non-invasive measurement of tumour hypoxia with positron emission tomography, magnetic resonance imaging and other imaging modalities. Here, we describe the complexities of defining and measuring tumour hypoxia and highlight the therapeutic approaches to combat it. © 2014 The Royal College of Radiologists. Source

Cawthorne C.,Wolfson Molecular Imaging Center | Cawthorne C.,University of Hull | Burrows N.,Hypoxia and Therapeutics Group | Gieling R.G.,Hypoxia and Therapeutics Group | And 16 more authors.
Molecular Cancer Therapeutics | Year: 2013

The phosphoinositide 3-kinase (PI3K) pathway is deregulated in a range of cancers, and several targeted inhibitors are entering the clinic. This study aimed to investigate whether the positron emission tomography tracer 3′-deoxy-3′-[18F]fluorothymidine ([18F]-FLT) is suitable to mark the effect of the novel PI3K inhibitor GDC-0941, which has entered phase II clinical trial. CBA nude mice bearing U87 glioma and HCT1 16 colorectal xenografts were imaged at baseline with [18F]-FLT and at acute (18 hours) and chronic (186 hours) time points after twice-daily administration of GDC-0941 (50 mg/kg) or vehicle. Tumor uptake normalized to blood pool was calculated, and tissue was analyzed at sacrifice for PI3K pathway inhibition and thymidine kinase (TK1) expression. Uptake of [ 18F]-FLT was also assessed in tumors inducibly overexpressing a dominant-negative form of the PI3K p85 subunit p85α, as well as HCT116 liver metastases after GDC-0941 therapy. GDC-0941 treatment induced tumor stasis in U87 xenografts, whereas inhibition of HCT116 tumors was more variable. Tumor uptake of [18F]-FLT was significantly reduced following GDC-0941 dosing in responsive tumors at the acute time point and correlated with pharmacodynamic markers of PI3K signaling inhibition and significant reduction in TK1 expression in U87, but not HCT116, tumors. Reduction of PI3K signaling via expression of Δp85α significantly reduced tumor growth and [18F]-FLT uptake, as did treatment of HCT116 liver metastases with GDC-0941. These results indicate that [18F]-FLT is a strong candidate for the noninvasive measurement of GDC-0941 action. ©2013 American Association for Cancer Research. Source

Fairclough M.,Wolfson Molecular Imaging Center | Prenant C.,Wolfson Molecular Imaging Center | Ellis B.,University of Manchester | Boutin H.,Wolfson Molecular Imaging Center | And 4 more authors.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2016

Mixed leukocyte (white blood cells [WBCs]) trafficking using positron emission tomography (PET) is receiving growing interest to diagnose and monitor inflammatory conditions. PET, a high sensitivity molecular imaging technique, allows precise quantification of the signal produced from radiolabelled moieties. We have evaluated a new method for radiolabelling WBCs with either zirconium-89 (89Zr) or copper-64 (64Cu) for PET imaging. Chitosan nanoparticles (CNs) were produced by a process of ionotropic gelation and used to deliver radiometals into WBCs. Experiments were carried out using mixed WBCs freshly isolated from whole human blood. WBCs radiolabelling efficiency was higher with [89Zr]-loaded CN (76.8 ± 9.6% (n = 12)) than with [64Cu]-loaded CN (26.3 ± 7.0 % (n = 7)). [89Zr]-WBCs showed an initial loss of 28.4 ± 5.8% (n = 2) of the radioactivity after 2 h. This loss was then followed by a plateau as 89Zr remains stable in the cells. [64Cu]-WBCs showed a loss of 85 ± 6% (n = 3) of the radioactivity after 1 h, which increased to 96 ± 6% (n = 3) loss after 3 h. WBC labelling with [89Zr]-loaded CN showed a fast kinetic of leukocyte association, high labelling efficiency and a relatively good retention of the radioactivity. This method using 89Zr has a potential application for PET imaging of inflammation. Copyright © 2016 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons, Ltd. Source

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