351 results found
Veronese M, Rizzo G, Aboagye EO, et al., 2014, Parametric imaging of F-18-fluoro-3-deoxy-3-L-fluorothymidine PET data to investigate tumour heterogeneity, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 41, Pages: 1781-1792, ISSN: 1619-7070
Witney TH, Pisaneschi F, Alam IS, et al., 2014, Preclinical Evaluation of 3-F-18-Fluoro-2,2-Dimethylpropionic Acid as an Imaging Agent for Tumor Detection, JOURNAL OF NUCLEAR MEDICINE, Vol: 55, Pages: 1506-1512, ISSN: 0161-5505
Lavdas I, Miquel ME, McRobbie DW, et al., 2014, Comparison Between Diffusion-Weighted MRI (DW-MRI) at 1.5 and 3 Tesla: A Phantom Study, JOURNAL OF MAGNETIC RESONANCE IMAGING, Vol: 40, Pages: 682-690, ISSN: 1053-1807
Gallo J, Kamaly N, Lavdas I, et al., 2014, CXCR4-Targeted and MMP-Responsive Iron Oxide Nanoparticles for Enhanced Magnetic Resonance Imaging, Angewandte Chemie International Edition, Vol: 53, Pages: 9550-9554, ISSN: 1521-3773
MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these ‘smart’ self-assembling nanomaterials.
Evans HL, Quang-De N, Carroll LS, et al., 2014, A bioorthogonal Ga-68-labelling strategy for rapid in vivo imaging, CHEMICAL COMMUNICATIONS, Vol: 50, Pages: 9557-9560, ISSN: 1359-7345
Kenny LM, Tomasi G, Turkheimer F, et al., 2014, Preliminary clinical assessment of the relationship between tumor alphavbeta3 integrin and perfusion in patients studied with [F-18]fluciclatide kinetics and [O-15]H2O PET, EJNMMI RESEARCH, Vol: 4, ISSN: 2191-219X
Alam IS, Witney TH, Tomasi G, et al., 2014, Radiolabeled RGD Tracer Kinetics Annotates Differential alpha(v)beta(3) Integrin Expression Linked to Cell Intrinsic and Vessel Expression, MOLECULAR IMAGING AND BIOLOGY, Vol: 16, Pages: 558-566, ISSN: 1536-1632
Sala R, Quang-De N, Patel CBK, et al., 2014, Phosphorylation Status of Thymidine Kinase 1 Following Antiproliferative Drug Treatment Mediates 3 '-Deoxy-3 '-[F-18]-Fluorothymidine Cellular Retention, PLOS ONE, Vol: 9, ISSN: 1932-6203
Witney TH, Fortt RR, Aboagye EO, 2014, Correction: Preclinical assessment of carboplatin treatment efficacy in lung cancer by<sup>18</sup>F-ICMT-11-positron emission tomography (PLoS ONE (2014) 9, 3 (e91694) DOI: 10.1371/journal.pone.0091694), PLoS ONE, Vol: 9
Mapelli P, Tam HH, Sharma R, et al., 2014, Frequency and significance of physiological versus pathological uptake of Ga-68-DOTATATE in the pancreas: validation with morphological imaging, NUCLEAR MEDICINE COMMUNICATIONS, Vol: 35, Pages: 613-619, ISSN: 0143-3636
Schelhaas S, Wachsmuth L, Viel T, et al., 2014, Variability of Proliferation and Diffusion in Different Lung Cancer Models as Measured by 3'-Deoxy-3'-F-18-Fluorothymidine PET and Diffusion-Weighted MR Imaging, JOURNAL OF NUCLEAR MEDICINE, Vol: 55, Pages: 983-988, ISSN: 0161-5505
Evans HL, Carroll L, Aboagye EO, et al., 2014, Bioorthogonal chemistry for Ga-68 radiolabelling of DOTA-containing compounds, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol: 57, Pages: 291-297, ISSN: 0362-4803
Trousil S, Hoppmann S, Quang-De N, et al., 2014, Positron Emission Tomography Imaging with F-18-Labeled Z(HER2:2891) Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies, CLINICAL CANCER RESEARCH, Vol: 20, Pages: 1632-1643, ISSN: 1078-0432
Witney TH, Fortt RR, Aboagye EO, 2014, Preclinical Assessment of Carboplatin Treatment Efficacy in Lung Cancer by F-18-ICMT-11-Positron Emission Tomography, PLOS ONE, Vol: 9, ISSN: 1932-6203
Witney TH, Carroll L, Alam IS, et al., 2014, A Novel Radiotracer to Image Glycogen Metabolism in Tumors by Positron Emission Tomography, CANCER RESEARCH, Vol: 74, Pages: 1319-1328, ISSN: 0008-5472
Carroll L, Aboagye EO, 2014, A manganese-catalysed oxidative benzylic C-H F-18-fluorination for applications in drug development, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol: 57, Pages: 181-181, ISSN: 0362-4803
Aboagye EO, Aigbirhio FI, Allen P, et al., 2014, Abstracts of the 22nd International Isotope Society (UK Group) Symposium: synthesis and applications of labelled compounds 2013., J Labelled Comp Radiopharm, Vol: 57, Pages: 178-190
Meeting Summary The 22nd annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK, on Friday, 18 October 2013. The meeting was attended by 65 delegates from academia and industry; the life sciences; and chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral and poster presentations on isotopic chemistry and applications of labelled compounds, or of chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium programme was divided into a morning session chaired by Dr Karl Cable (GlaxoSmithKline, UK) and afternoon sessions chaired by Mr Mike Chappelle (Quotient Biosciences, UK) and by Dr Nick Bushby (AstraZeneca, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).
Challapalli A, Sharma R, Hallett WA, et al., 2014, Biodistribution and Radiation Dosimetry of Deuterium-Substituted F-18-Fluoromethyl-[1, 2-H-2(4)]Choline in Healthy Volunteers, JOURNAL OF NUCLEAR MEDICINE, Vol: 55, Pages: 256-263, ISSN: 0161-5505
Pisaneschi F, Slade RL, Iddon L, et al., 2014, Synthesis of a new fluorine-18 glycosylated 'click' cyanoquinoline for the imaging of epidermal growth factor receptor, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol: 57, Pages: 92-96, ISSN: 0362-4803
George GPC, Stevens E, Aberg O, et al., 2014, Preclinical evaluation of a CXCR4-specific Ga-68-labelled TN14003 derivative for cancer PET imaging, BIOORGANIC & MEDICINAL CHEMISTRY, Vol: 22, Pages: 796-803, ISSN: 0968-0896
Gallo J, Alam IS, Jin J, et al., 2014, PET imaging with multimodal upconversion nanoparticles, DALTON TRANSACTIONS, Vol: 43, Pages: 5535-5545, ISSN: 1477-9226
Challapalli A, Barwick T, Tomasi G, et al., 2014, Exploring the potential of [C-11]choline-PET/CT as a novel imaging biomarker for predicting early treatment response in prostate cancer, NUCLEAR MEDICINE COMMUNICATIONS, Vol: 35, Pages: 20-29, ISSN: 0143-3636
Merchant S, Witney TH, Aboagye EO, 2014, Imaging as a pharmacodynamic and response biomarker in cancer, Clinical and Translational Imaging, Vol: 2, Pages: 13-31, ISSN: 2281-5872
Imaging of biological and molecular processes has provided the platform for evaluating the hallmarks of cancer, such as metabolism, proliferation, tissue invasion, angiogenesis, apoptosis and hypoxia, and in turn for assessing the efficacy of treatments including novel targeted therapies. Cross-sectional imaging methods can measure response to chemotherapy and radiotherapy by measuring changes in tumour volume. Imaging modalities such as positron emission tomography and functional magnetic resonance imaging can non-invasively detect early molecular changes in response to therapy, provide guidance for therapy optimisation, and predict response to treatments and clinical outcome. In an era of escalating drug trial costs, with high attrition rates of early-phase studies, the development of an imaging biomarker can contribute to optimisation of proof of concept and patient stratification. In this review, we examine the current molecular imaging modalities used to assess pharmacodynamics and therapy response and highlight some novel emerging imaging strategies. © 2014 Italian Association of Nuclear Medicine and Molecular Imaging.
Lake MC, Aboagye EO, 2014, Luciferase fragment complementation imaging in preclinical cancer studies., Oncoscience, Vol: 1, Pages: 310-325, ISSN: 2331-4737
The luciferase fragment complementation assay (LFCA) enables molecular events to be non-invasively imaged in live cells in vitro and in vivo in a comparatively cheap and safe manner. It is a development of previous enzyme complementation assays in which reporter genes are split into two, individually enzymatically inactive, fragments that are able to complement one another upon interaction. This complementation can be used to externally visualize cellular activities. In recent years, the number of studies which have used LFCAs to probe questions relevant to cancer have increased, and this review summarizes the most significant and interesting of these. In particular, it focuses on work conducted on the epidermal growth factor, nuclear and chemokine receptor families, and intracellular signaling pathways, including IP3, cAMP, Akt, cMyc, NRF2 and Rho GTPases. LFCAs which have been developed to image DNA methylation and detect RNA transcripts are also discussed.
Gallo J, Alam IS, Lavdas I, et al., 2013, RGD-targeted MnO nanoparticles as T1 contrast agents for cancer imaging – the effect of PEG length in vivo, J. Mater. Chem. B
As magnetic resonance imaging (MRI) contrast agents, T1 Gd3+ chelates are generally the preferred option for radiologists over T2 iron oxide nanoparticles. The main reason for the popularity of T1 agents is the easier interpretation of T1-weighted MR images. However, the chemical versatility of nanoparticulate platforms makes them ideal candidates for the next generation of targeted MRI contrast agents. In this context, we present herein the design and preparation of a nanoparticulate contrast agent based on MnO, which presents T1 contrast enhancement properties as well as nanoparticle formulation. Functionalization of MnO nanoparticles with the extensively studied RGD peptide was used to target tumours over-expressing the αvβ3 integrin. PEG (polyethylene glycol) molecules were used to increase the blood half-life of the nanoparticles in vivo, and the effect of different PEG lengths on the final contrast on MR images was investigated.
Kaliszczak M, Pardo OE, Seckl MJ, et al., 2013, HDAC6 inhibitor C1A abrogates the recruitment of the autophagic machinery and synergizes with proteasome, src kinase, and PI3K-mTOR inhibition., MOLECULAR CANCER THERAPEUTICS, Vol: 12, ISSN: 1535-7163
Trousil S, Hoppmann S, Nguyen Q-D, et al., 2013, Positron emission tomography imaging of HER2 expression and pharmacodynamic response to HSP90 inhibition with the next-generation ZHER2:2891 Affibody molecule [18F]GE-226., MOLECULAR CANCER THERAPEUTICS, Vol: 12, ISSN: 1535-7163
Eccles SA, Aboagye EO, Ali S, et al., 2013, Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer, Breast Cancer Research, Vol: 15, Pages: R-R, ISSN: 1465-542X
IntroductionBreast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.MethodsMore than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.ResultsThe 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease
Pisaneschi F, Witney TH, Iddon L, et al., 2013, Synthesis of [F-18]fluoro-pivalic acid: an improved PET imaging probe for the fatty acid synthesis pathway in tumours, MEDCHEMCOMM, Vol: 4, Pages: 1350-1353, ISSN: 2040-2503
Kaliszczak M, Patel H, Kroll SHB, et al., 2013, Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance, British Journal of Cancer, Vol: 109, Pages: 2356-2367, ISSN: 1532-1827
background: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy.methods: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy.results: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å2) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively.conclusion: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer.
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