Imperial College London

ProfessorEricAboagye

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
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Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

GN1Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

332 results found

O'Connor JP, Aboagye EO, Adams JE, Aerts HJ, Barrington SF, Beer AJ, Boellaard R, Bohndiek SE, Brady M, Brown G, Buckley DL, Chenevert TL, Clarke LP, Collette S, Cook GJ, deSouza NM, Dickson JC, Dive C, Evelhoch JL, Faivre-Finn C, Gallagher FA, Gilbert FJ, Gillies RJ, Goh V, Griffiths JR, Groves AM, Halligan S, Harris AL, Hawkes DJ, Hoekstra OS, Huang EP, Hutton BF, Jackson EF, Jayson GC, Jones A, Koh DM, Lacombe D, Lambin P, Lassau N, Leach MO, Lee TY, Leen EL, Lewis JS, Liu Y, Lythgoe MF, Manoharan P, Maxwell RJ, Miles KA, Morgan B, Morris S, Ng T, Padhani AR, Parker GJ, Partridge M, Pathak AP, Peet AC, Punwani S, Reynolds AR, Robinson SP, Shankar LK, Sharma RA, Soloviev D, Stroobants S, Sullivan DC, Taylor SA, Tofts PS, Tozer GM, van Herk M, Walker-Samuel S, Wason J, Williams KJ, Workman P, Yankeelov TE, Brindle KM, McShane LM, Jackson A, Waterton JCet al., 2016, Imaging biomarker roadmap for cancer studies, Nature Reviews Clinical Oncology, Vol: 14, Pages: 169-186, ISSN: 1759-4782

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Journal article

Glocker B, Konukoglu E, Lavdas I, Iglesias JE, Aboagye EO, Rockall AG, Rueckert Det al., 2016, Correction of Fat-Water Swaps in Dixon MRI, 19th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2016), Publisher: Springer Verlag, ISSN: 0302-9743

The Dixon method is a popular and widely used technique for fat-water separation in magnetic resonance imaging, and today, nearly all scanner manufacturers are offering a Dixon-type pulse sequence that produces scans with four types of images: in-phase, out-of-phase, fat-only, and water-only. A natural ambiguity due to phase wrapping and local minima in the optimization problem cause a frequent artifact of fat-water inversion where fat- and water-only voxel values are swapped. This artifact affects up to 10 % of routinely acquired Dixon images, and thus, has severe impact on subsequent analysis. We propose a simple yet very effective method, Dixon-Fix, for correcting fat-water swaps. Our method is based on regressing fat- and water-only images from in- and out-of-phase images by learning the conditional distribution of image appearance. The predicted images define the unary potentials in a globally optimal maximum-a-posteriori estimation of the swap labeling with spatial consistency. We demonstrate the effectiveness of our approach on whole-body MRI with various types of fat-water swaps.

Conference paper

Dubash SR, Keat N, Mapelli P, Twyman F, Carroll L, Kozlowski K, Al-Nahhas A, Saleem A, Huiban M, Frilling A, Barwick T, Rockall A, Sharma R, Aboagye EOet al., 2016, Biodistribution, radiation dosimetry and first preliminary results of a novel F-18-fluoroethyl triazole [Tyr(3)] octreotate analogue for PET imaging in locally advanced and metastatic Neuroendocrine tumour patients, Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S105-S105, ISSN: 1619-7070

Conference paper

Slade RL, Pisaneschi F, Nguyen QD, Smith G, Carroll L, Beckley A, Kaliszczak MA, Aboagye EOet al., 2016, Identification of ABC Transporter Interaction of a Novel Cyanoquinoline Radiotracer and Implications for Tumour Imaging by Positron Emission Tomography, PLOS One, Vol: 11, ISSN: 1932-6203

BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed in many cancers including lung, ovarian, breast, head and neck and brain. Mutation of this receptor has been shown to play a crucial role in the response of non-small cell lung carcinoma (NSCLC) to EGFR-targeted therapies. It is envisaged that imaging of EGFR using positron emission tomography (PET) could aid in selection of patients for treatment with novel inhibitors. We recognised multi-drug resistant phenotype as a threat to development of successful imaging agents. In this report, we describe discovery of a novel cyanoquinoline radiotracer that lacks ABC transporter activity. METHODS: Cellular retention of the prototype cyanoquinoline [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxyquinolin-6-yl}-4-({[1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl]methyl}amino)-but-2-enamide ([18F]FED6) and [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxyquinolin-6-yl}-4-[({1-[(2R,5S)-3-fluoro-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]-1H-1,2,3-triazol-4-yl}methyl)amino]but-2-enamide ([18F]FED20) were evaluated to establish potential for imaging specificity. The substrate specificity of a number of cyanoquinolines towards ABC transporters was investigated in cell lines proficient or deficient in ABCB1 or ABCG2. RESULTS: FED6 demonstrated substrate specificity for both ABCG2 and ABCB1, a property that was not observed for all cyanoquinolines tested, suggesting scope for designing novel probes. ABC transporter activity was confirmed by attenuating the activity of transporters with drug inhibitors or siRNA. We synthesized a more hydrophilic compound [18F]FED20 to overcome ABC transporter activity. FED20 lacked substrate specificity for both ABCB1 and ABCG2, and maintained a strong affinity for EGFR. Furthermore, FED20 showed higher inhibitory affinity for active mutant EGFR versus wild-type or resistant mutant EGFR; this property resulted in higher [18F]FED20 cellular retention in acti

Journal article

Ali S, Patel H, Periyasamy M, Bondke A, Slafer BW, Ottaviani S, Harrod A, Buluwela L, Fuchter MJ, Barrett AGM, Coombes RCet al., 2016, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for breast cancer, UK Breast Cancer Research Symposium, Publisher: Springer Verlag, Pages: 195-195, ISSN: 0167-6806

Conference paper

Heinzmann K, Honess DJ, Lewis DY, Smith DM, Cawthorne C, Keen H, Heskamp S, Schelhaas S, Witney TH, Soloviev D, Williams KJ, Jacobs AH, Aboagye EO, Griffiths JR, Brindle KMet al., 2016, The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models, EJNMMI Research, Vol: 6, ISSN: 2191-219X

BACKGROUND: Recent studies have shown that 3'-deoxy-3'-[(18)F] fluorothymidine ([(18)F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [(18)F]FLT uptake across a broad spectrum of murine cancer models. A modified liquid chromatography-mass spectrometry (LC-MS/MS) method was used to determine endogenous thymidine concentrations in plasma and tissues of tumour-bearing and non-tumour bearing mice and rats. Thymidine concentrations were determined in 22 tumour models, including xenografts, syngeneic and spontaneous tumours, from six research centres, and a subset was compared for [(18)F]FLT uptake, described by the maximum and mean tumour-to-liver uptake ratio (TTL) and SUV. RESULTS: The LC-MS/MS method used to measure thymidine in plasma and tissue was modified to improve sensitivity and reproducibility. Thymidine concentrations determined in the plasma of 7 murine strains and one rat strain were between 0.61 ± 0.12 μM and 2.04 ± 0.64 μM, while the concentrations in 22 tumour models ranged from 0.54 ± 0.17 μM to 20.65 ± 3.65 μM. TTL at 60 min after [(18)F]FLT injection, determined in 14 of the 22 tumour models, ranged from 1.07 ± 0.16 to 5.22 ± 0.83 for the maximum and 0.67 ± 0.17 to 2.10 ± 0.18 for the mean uptake. TTL did not correlate with tumour thymidine concentrations. CONCLUSIONS: Endogenous tumour thymidine concentrations alone are not predictive of [(18)F]FLT uptake in murine cancer models.

Journal article

Theodorou IG, Jawad Z, Qin H, Aboagye EO, Porter A, Ryan M, Xie Fet al., 2016, Significant metal enhanced fluorescence of Ag2S quantum dots in the second near-infrared window, Nanoscale, Vol: 8, Pages: 12869-12873, ISSN: 2040-3372

The amplification of light in NIR-II from Ag2S QDs via metal enhanced fluorescence (MEF) is reported for the first time. Significant fluorescence enhancement of over 100 times for Ag2S QDs deposited on Au-nanostructured arrays, paves the way for novel sensing and imaging applications based on Ag2S QDs, with improved detection sensitivity and contrast enhancement.

Journal article

Favicchio R, Angelopoulos N, Brickute D, Fortt R, Twyman F, Giamas G, Lacal JC, Aboagye EOet al., 2016, Choline metabolism is an early predictor of EGFR-mediated survival in NSCLC, AACR 107th Annual Meeting on Bioinformatics and Systems Biology, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Kaliszczak M, Trousil S, Ali T, Aboagye EOet al., 2016, AKT activation controls cell survival in response to HDAC6 inhibition., Cell Death & Disease, Vol: 7, ISSN: 2041-4889

HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug-induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3'-kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors.

Journal article

Merchant S, Allott L, Carroll L, Tittrea V, Kealey S, Witney TH, Miller PW, Smith G, Aboagye EOet al., 2016, Synthesis and pre-clinical evaluation of a [<sup>18</sup>F]fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression, RSC Advances, Vol: 6, Pages: 57569-57579, ISSN: 2046-2069

The estrogen receptor (ER) and progesterone receptor (PR) are over-expressed in ∼50% of breast cancer lesions, and used as biomarkers to stratify patients for endocrine therapy. Currently, immunohistochemical (IHC) assessment of these lesions from a core-needle biopsy in deep-sited metastases has limitations associated with sampling error and lack of standardization. An alternative solution is positron emission tomography (PET)-based probes, which are inherently quantitative and capable of imaging the entire tumor, including metastases. This work features the synthesis and biological evaluation of a novel fluorinated derivative of tanaproget, a high affinity non-steroidal PR ligand, as a candidate for imaging PR expression in vivo. Radiolabeling of the candidate was achieved in a 15% ± 4 radiochemical yield (non-decay corrected) in one step from [18F]fluoromethyltosylate in 30 min. Cell uptake studies showed a significant difference between the radioligand uptake in PR+ and PR- cell lines; however, in vivo imaging was confounded by defluorination hypothesized to occur via iminium salt formation. Investigation into high affinity, metabolically stable non-steroidal PR ligands is currently ongoing.

Journal article

Trousil S, Kaliszczak M, Schug Z, Nguyen Q, Tomasi G, Favicchio R, Brickute D, Fortt R, Twyman FJ, Carroll L, Kalusa A, Navaratnam N, Adejumo T, Carling D, Gottlieb E, Aboagye EOet al., 2016, The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth., Oncotarget, Vol: 7, Pages: 37103-37120, ISSN: 1949-2553

The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2-2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids.

Journal article

Dubash S, Keat N, Mapelli P, Twyman F, Carroll L, Kozlowski K, Al-Nahhas A, Saleem A, Huiban M, Janisch R, Frilling A, Sharma R, Aboagye EOet al., 2016, Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors, Journal of Nuclear Medicine, Vol: 57, Pages: 1207-1213, ISSN: 1535-5667

We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137–163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed whole-body PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.

Journal article

Peck B, Schug ZT, Zhang Q, Dankworth B, Jones DT, Smethurst E, Patel R, Mason S, Jiang M, Saunders R, Howell M, Mitter R, Spencer-Dene B, Stamp G, McGarry L, James D, Shanks E, Aboagye EO, Critchlow SE, Leung HY, Harris AL, Wakelam MJ, Gottlieb E, Schulze Aet al., 2016, Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments, Cancer and Metabolism, Vol: 4, ISSN: 2049-3002

Journal article

Hoogenboom TC, Thursz M, Aboagye EO, Sharma Ret al., 2016, Functional imaging of hepatocellular carcinoma, HEPATIC ONCOLOGY, Vol: 3, Pages: 137-153, ISSN: 2045-0923

Journal article

Aboagye EO, Challapalli A, 2016, Positron emission tomography imaging of tumor cell metabolism and application to therapy response monitoring, Frontiers in Oncology, Vol: 6, ISSN: 2234-943X

Cancer cells do reprogram their energy metabolism to enable several functions, such as generation of biomass including membrane biosynthesis, and overcoming bioenergetic and redox stress. In this article, we review both established and evolving radioprobes developed in association with positron emission tomography (PET) to detect tumor cell metabolism and effect of treatment. Measurement of enhanced tumor cell glycolysis using 2-deoxy-2-[18F]fluoro-D-glucose is well established in the clinic. Analogs of choline, including [11C]choline and various fluorinated derivatives are being tested in several cancer types clinically with PET. In addition to these, there is an evolving array of metabolic tracers for measuring intracellular transport of glutamine and other amino acids or for measuring glycogenesis, as well as probes used as surrogates for fatty acid synthesis or precursors for fatty acid oxidation. In addition to providing us with opportunities for examining the complex regulation of reprogramed energy metabolism in living subjects, the PET methods open up opportunities for monitoring pharmacological activity of new therapies that directly or indirectly inhibit tumor cell metabolism.

Journal article

Alam IS, Arrowsmith RL, Cortezon-Tamarit F, Twyman F, Kociok-Koehn G, Botchway SW, Dilworth JR, Carroll L, Aboagye EO, Pascu SIet al., 2016, Correction: Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia, Dalton Transactions, Vol: 45, Pages: 3650-3650, ISSN: 1477-9226

Journal article

Mazarico JM, Sánchez-Arévalo Lobo VJ, Favicchio R, Greenhalf W, Costello E, Carrillo-de Santa Pau E, Marqués M, Lacal JC, Aboagye E, Real FXet al., 2016, Choline Kinase Alpha (CHKα) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors., Molecular Cancer Therapeutics, Vol: 15, Pages: 323-333, ISSN: 1538-8514

Choline kinase α (CHKα) plays a crucial role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. We have analyzed the expression of CHKα in cell lines derived from pancreatic ductal adenocarcinoma (PDAC) and have found increased CHKα expression, associated with differentiation. CHKα protein expression was directly correlated with sensitivity to MN58b, a CHKα inhibitor that reduced cell growth through the induction of apoptosis. Accordingly, CHKα knockdown led to reduced drug sensitivity. In addition, we found that gemcitabine-resistant PDAC cells displayed enhanced sensitivity to CHKα inhibition and, in vitro, MN58b had additive or synergistic effects with gemcitabine, 5-fluorouracil, and oxaliplatin, three active drugs in the treatment of PDAC. Using tissue microarrays, CHKα was found to be overexpressed in 90% of pancreatic tumors. While cytoplasmic CHKα did not relate to survival, nuclear CHKα distribution was observed in 43% of samples and was associated with longer survival, especially among patients with well/moderately differentiated tumors. To identify the mechanisms involved in resistance to CHKα inhibitors, we cultured IMIM-PC-2 cells with increasingly higher concentrations of MN58b and isolated a subline with a 30-fold higher IC50. RNA-Seq analysis identified upregulation of ABCB1 and ABCB4 multidrug resistance transporters, and functional studies confirmed that their upregulation is the main mechanism involved in resistance. Overall, our findings support the notion that CHKα inhibition merits further attention as a therapeutic option in patients with PDAC and that expression levels may predict response. Mol Cancer Ther; 15(2); 323-33. ©2016 AACR.

Journal article

Alam IS, Arrowsmith RL, Cortezon-Tamarit F, Twyman F, Kociok-Koehn G, Botchway SW, Dilworth JR, Carroll L, Aboagye EO, Pascu SIet al., 2016, Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia, Dalton Transactions, Vol: 45, Pages: 144-155, ISSN: 1477-9226

We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under ‘cold’ and ‘hot’ biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. 68Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration.

Journal article

Hopkins TG, Blagden S, Mura M, Ghaem-maghami Set al., 2015, The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer, Nucleic Acids Research, Vol: 44, Pages: 1227-1246, ISSN: 1362-4962

RNA-binding proteins (RBPs) are increasingly identifiedas post-transcriptional drivers of cancer progression.The RBP LARP1 is an mRNA stability regulator,and elevated expression of the protein in hepatocellularand lung cancers is correlated with adverseprognosis. LARP1 associates with an mRNA interactomethat is enriched for oncogenic transcripts.Here we explore the role of LARP1 in epithelial ovariancancer, a disease characterized by the rapid acquisitionof resistance to chemotherapy through theinduction of pro-survival signalling. We show, usingovarian cell lines and xenografts, that LARP1 is requiredfor cancer cell survival and chemotherapy resistance.LARP1 promotes tumour formation in vivoand maintains cancer stem cell-like populations. Usingtranscriptomic analysis following LARP1 knockdown,cross-referenced against the LARP1 interactome,we identify BCL2 and BIK as LARP1 mRNAtargets. We demonstrate that, through an interactionwith the 3 untranslated regions (3 UTRs) of BCL2and BIK, LARP1 stabilizes BCL2 but destabilizes BIKwith the net effect of resisting apoptosis. Together,our data indicate that by differentially regulating thestability of a selection of mRNAs, LARP1 promotesovarian cancer progression and chemotherapy resistance.

Journal article

Sharma R, Kallur KG, Ryu JS, Parameswaran RV, Lindman H, Avril N, Gleeson FV, Lee JD, Lee K-H, O'Doherty MJ, Groves AM, Miller MP, Somer EJ, Coombes CR, Aboagye EOet al., 2015, Multicenter Reproducibility of F-18-Fluciclatide PET Imaging in Subjects with Solid Tumors, JOURNAL OF NUCLEAR MEDICINE, Vol: 56, Pages: 1855-1861, ISSN: 0161-5505

Journal article

Allott L, Smith G, Aboagye EO, Carroll Let al., 2015, PET imaging of steroid hormone receptor expression, Molecular Imaging, Vol: 14, Pages: 534-550, ISSN: 1536-0121

Journal article

Da Pieve C, Allott L, Martins CD, Carroll L, Paul RL, Aboagye EO, Kramer-Marek G, Smith Get al., 2015, Strategies for the development of high specific activity affibody based probes for the detection of HER3 positive tumours, 28th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S247-S248, ISSN: 1619-7070

Conference paper

Challapalli A, Trousil S, Hazell S, Kozlowski K, Gudi M, Aboagye EO, Mangar Set al., 2015, Exploiting altered patterns of choline kinase-alpha expression on human prostate tissue to prognosticate prostate cancer, JOURNAL OF CLINICAL PATHOLOGY, Vol: 68, Pages: 703-709, ISSN: 0021-9746

Journal article

Mapelli P, Aboagye EO, Stebbing J, Sharma Ret al., 2015, Epigenetic changes in gastroenteropancreatic neuroendocrine tumours, ONCOGENE, Vol: 34, Pages: 4439-4447, ISSN: 0950-9232

Journal article

Lavdas I, Rockall AG, Castelli F, Sandhu RS, Papadaki A, Honeyfield L, Waldman AD, Aboagye EOet al., 2015, Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From Whole-Body DWI at 1.5 T: The Effect of Sex and Age, AMERICAN JOURNAL OF ROENTGENOLOGY, Vol: 205, Pages: 242-250, ISSN: 0361-803X

Journal article

Doepner AM, Aboagye EO, Barrett AGM, 2015, 2 '-Deoxy-2 ',2 '-difluorothymidine analogues for radiolabeling with fluorine-18 and other biomedical applications, TETRAHEDRON LETTERS, Vol: 56, Pages: 3293-3297, ISSN: 0040-4039

Journal article

Carroll L, Evans H, Spivey AC, Aboagye EOet al., 2015, Mn-salen catalysed benzylic C-H activation for the synthesis of aryl [(18)F]CF3-containing PET probes., Chemical Communications, Vol: 51, Pages: 8439-8441, ISSN: 1364-548X

The development of a Mn-salen complex catalysed oxidative benzylic fluorination of non-activated C-H bonds using [(18)F]fluoride is described for installation of [(18)F]CHRF, [(18)F]CR2F and particularly [(18)F]CF3 containing groups in the presence of other functional groups.

Journal article

Merchant S, Aboagye EO, Lim A, Kozlowski K, Patel N, Steel J, Cleator S, Shousha S, Varghese V, Coombes RC, Kenny Let al., 2015, Evaluation of apoptosis in breast cancer using the novel PET probe [F-18]ICMT-11 in patients treated with neoadjuvant FEC chemotherapy: Initial assessment of optimum imaging time and relation to caspase-3 immunostaining, 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Challapalli A, Barwick T, Pearson RA, Merchant S, Mauri F, Howell EC, Sumpter K, Maxwell RJ, Aboagye EO, Sharma Ret al., 2015, 3 '-Deoxy-3 '-F-18-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 42, Pages: 831-840, ISSN: 1619-7070

Journal article

Saleem A, Searle GE, Kenny LM, Huiban M, Kozlowski K, Waldman AD, Woodley L, Palmieri C, Lowdell C, Kaneko T, Murphy PS, Lau MR, Aboagye EO, Coombes RCet al., 2015, Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer, EJNMMI Research, Vol: 5, ISSN: 2191-219X

BackgroundBrain metastases are common in human epidermal growth factor receptor (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain is key to management of cranial disease. In this study, positron emission tomography (PET) scanning after administration of radiolabelled lapatinib was used to obtain direct evidence of cranial drug access.MethodsPatients with Her-2+ metastatic breast cancer either with at least one 1-cm diameter brain metastasis or without brain metastases underwent dynamic carbon-11 radiolabelled lapatinib ([11C]lapatinib)-PET. Less than 20 μg of [11C]lapatinib was administered before and after 8 days of oral lapatinib (1,500 mg once daily). Radial arterial blood sampling was performed throughout the 90-min scan. The contribution of blood volume activity to the tissue signal was excluded to calculate lapatinib uptake in normal brain and metastases. Partitioning of radioactivity between plasma and tissue (V T) was calculated and the tissue concentration of lapatinib derived. Plasma lapatinib levels were measured and adverse events noted.ResultsSix patients (three with brain metastases) were recruited. About 80% plasma radioactivity corresponded to intact [11C]lapatinib after 60 min. PET signal in the brain corresponded to circulating radioactivity levels, with no [11C]lapatinib uptake observed in normal brain tissue. In contrast, radioactivity uptake in cranial metastases was significantly higher (p = 0.002) than that could be accounted by circulating radioactivity levels, consistent with [11C]lapatinib uptake in brain metastases. There was no difference in lapatinib uptake between the baseline and day 8 scans, suggesting no effect of increased drug access by inhibition of the drug efflux proteins by therapeutic doses of lapatinib.ConclusionsIncreased lapatinib uptake was observed in brain metastases but not in normal brain.

Journal article

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