Imperial College London

ProfessorEricAboagye

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
//

Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
//

Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
//

Location

 

GN1Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

351 results found

Leow CH, Marta B, Stanziola A, Hernandez-Gil J, Long NJ, Aboagye EO, Tang M-Xet al., 2017, Multi-Frame Rate Plane Wave Contrast-Enhance Ultrasound Imaging for Tumour Vasculature Imaging and Perfusion Quantification, IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719

A multi-frame rate plane wave imaging strategy is developed to simultaneously image tumor vasculature and quantify tumor perfusion. Customised imaging sequences interleaving a short but high frame rate (HFR) plane wave imaging sequence with a long but low frame rate imaging (LFR) sequence were implemented using a programmable ultrasound research platform. The results from a spatio-temporal coherence processing technique of ours demonstrated a significant improvement in the SNR and vasculature contrast when compared with the existing ultrafast Power Doppler (PD) using the same data. Initial perfusion quantification using LFR imaging was also demonstrated. Mean time intensity curve and some parametric measures were generated. Combining both structural and functional perfusion imaging using the multiframe rate sequences, a better evaluation of the tumour angiogenesis can be assessed.

Conference paper

Leow CH, Braga M, Hernandez-Gil J, Long NJ, Aboagye EO, Tang MXet al., 2017, Multi-frame rate plane wave contrast-enhanced ultrasound imaging for tumour vascular imaging and perfusion quantification, IEEE International Ultrasonics Symposium, IUS, Publisher: IEEE, ISSN: 1948-5719

Angiogenesis and blood flow dynamics play an important role in the development of malignant tumours and their response to treatment. While contrast enhanced ultrasound (CEUS) imaging with microbubble contrast agents as a tool for imaging angiogenesis and flow dynamics has shown great potential [1], recent development of plane wave high frame-rate (HFR) CEUS has offered new opportunities in such applications. In this study, we demonstrate an interleaved multi-frame rate plane wave CEUS imaging to quantify perfusion and to image vascular structure with improved resolution and contrast.

Conference paper

Dubash SR, Merchant S, Mauri F, Kozlowski K, Lim A, Patel N, Steel J, Heinzmann K, Azeem S, Cleator S, Coombes RC, Aboagye EO, Kenny Let al., 2017, Clinical translation of the caspase 3/7 specific PET radiotracer [F-18]ICMT-11 for measuring chemotherapy induced apoptosis in breast and lung cancer, Publisher: SPRINGER, Pages: S378-S379, ISSN: 1619-7070

Conference paper

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., 2017, Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer (vol 5, 30, 2015), EJNMMI RESEARCH, Vol: 7, ISSN: 2191-219X

Journal article

Heinzmann K, Carter LM, Lewis JS, Aboagye EOet al., 2017, Multiplexed imaging for diagnosis and therapy, Nature Biomedical Engineering, Vol: 1, Pages: 697-713

Complex molecular and metabolic phenotypes depict cancers as a constellation of different diseases with common themes. Precision imaging of such phenotypes requires flexible and tunable modalities capable of identifying phenotypic fingerprints by using a restricted number of parameters while ensuring sensitivity to dynamic biological regulation. Common phenotypes can be detected by in vivo imaging technologies, and effectively define the emerging standards for disease classification and patient stratification in radiology. However, for the imaging data to accurately represent a complex fingerprint, the individual imaging parameters need to be measured and analysed in relation to their wider spatial and molecular context. In this respect, targeted palettes of molecular imaging probes facilitate the detection of heterogeneity in oncogene-driven alterations and their response to treatment, and lead to the expansion of rational-design elements for the combination of imaging experiments. In this Review, we evaluate criteria for conducting multiplexed imaging, and discuss its opportunities for improving patient diagnosis and the monitoring of therapy.

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., 2017, Erratum to: Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer., EJNMMI Research, Vol: 7, Pages: 74-74, ISSN: 2191-219X

Journal article

Theodorou I, Jawad Z, Jiang Q, Aboagye E, Porter A, Ryan M, Xie Fet al., 2017, Gold Nanostar Substrates for Metal Enhanced Fluorescence through the First and Second Near-Infrared Windows, Chemistry of Materials, Vol: 29, Pages: 6916-6926, ISSN: 1520-5002

Gold nanostars (AuNSs) are receiving increasing attention for their potential applications in bionanotechnology because of their unique optical properties related to their complex branched morphology. Their sharp features allow strong localized surface plasmon resonances, tunable in the near-infrared (NIR) region, and large enhancements of local electromagnetic fields. Here, the application of AuNSs in metal-enhanced fluorescence (MEF) in the NIR and second NIR (NIR-II) biological windows is explored for the first time. NIR/NIR-II fluorophores are incorporated onto monolayers of AuNSs with tunable plasmonic responses. Over 320-fold fluorescence enhancement is achieved in the NIR, confirming that AuNS substrates are promising NIR-MEF platforms for the development of ultrasensitive biosensing applications. Using fluorescence lifetime measurements to semiquantitatively deconvolute the excitation enhancement from emission enhancement, as well as modeling to simulate the electric field enhancement, we show that a combination of enhanced excitation and an increased radiative decay rate, accompanied by an increase in the quantum yield, contribute to the observed large enhancement. AuNSs with different morphological features exhibit significantly different excitation enhancements, indicating the important role of the particle morphology on the magnitude of electromagnetic field enhancement and the resulting enhancement factor. Importantly, enhancement factors of up to 50-fold are also achieved in the NIR-II region, suggesting that this system holds promise for the future development of bright probes for NIR/NIR-II biosensing and bioimaging.

Journal article

Lavdas I, Glocker B, Kamnitsas K, Rueckert D, Mair H, Sandhu A, Taylor SA, Aboagye EO, Rockall AGet al., 2017, Fully automatic, multi-organ segmentation in normal whole body magnetic resonance imaging (MRI), using classification forests (CFs), convolutional neural networks (CNNs) and a multi-atlas (MA) approach., Medical Physics, Vol: 44, Pages: 5210-5220, ISSN: 0094-2405

PURPOSE: As part of a programme to implement automatic lesion detection methods for whole body magnetic resonance imaging (MRI) in oncology, we have developed, evaluated and compared three algorithms for fully automatic, multi-organ segmentation in healthy volunteers. METHODS: The first algorithm is based on classification forests (CFs), the second is based on 3D convolutional neural networks (CNNs) and the third algorithm is based on a multi-atlas (MA) approach. We examined data from 51 healthy volunteers, scanned prospectively with a standardised, multi-parametric whole body MRI protocol at 1.5T. The study was approved by the local ethics committee and written consent was obtained from the participants. MRI data were used as input data to the algorithms, while training was based on manual annotation of the anatomies of interest by clinical MRI experts. Five-fold cross-validation experiments were run on 34 artefact-free subjects. We report three overlap and three surface distance metrics to evaluate the agreement between the automatic and manual segmentations, namely the Dice similarity coefficient (DSC), recall (RE), precision (PR), average surface distance (ASD), root mean square surface distance (RMSSD) and Hausdorff distance (HD). Analysis of variances was used to compare pooled label metrics between the three algorithms and the DSC on a 'per-organ' basis. A Mann-Whitney U test was used to compare the pooled metrics between CFs and CNNs and the DSC on a 'per-organ' basis, when using different imaging combinations as input for training. RESULTS: All three algorithms resulted in robust segmenters that were effectively trained using a relatively small number of data sets, an important consideration in the clinical setting. Mean overlap metrics for all the segmented structures were: CFs: DSC=0.70±0.18, RE=0.73±0.18, PR=0.71±0.14, CNNs: DSC=0.81±0.13, RE=0.83±0.14, PR=0.82±0.10, MA: DSC=0.71±0.22, RE=0.70±0.34

Journal article

Calsolaro V, Femminella G, Fan Z, Dani M, Kozlowski K, Aboagye E, Edison Pet al., 2017, Evaluation of caspase-3 activation in an Alzheimer’s disease population using [18F]ICMT-11 PET/CT, Alzheimer's and Dementia, Vol: 13, Pages: P1353-P1354, ISSN: 1552-5260

Journal article

Aboagye EO, Kraeber-Bodéré F, 2017, Highlights lecture EANM 2016: "Embracing molecular imaging & multi-modal imaging: a smart move for nuclear medicine towards personalised medicine", European Journal of Nuclear Medicine and Molecular Imaging, Vol: 44, Pages: 1559-1574, ISSN: 1619-7089

The 2016 EANM Congress took place in Barcelona, Spain, from 15 to 19 October under the leadership of Prof. Wim Oyen, chair of the EANM Scientific Committee. With more than 6,000 participants, this congress was the most important European event in nuclear medicine, bringing together a multidisciplinary community involved in the different fields of nuclear medicine. There were over 600 oral and 1,200 poster or e-Poster presentations with an overwhelming focus on development and application of imaging for personalized care, which is timely for the community. Beyond FDG PET, major highlights included progress in the use of PSMA and SSTR receptor-targeted radiopharmaceuticals and associated theranostics in oncology. Innovations in radiopharmaceuticals for imaging pathologies of the brain and cardiovascular system, as well as infection and inflammation, were also highlighted. In the areas of physics and instrumentation, multimodality imaging and radiomics were highlighted as promising areas of research.

Journal article

Sharma R, Wang WM, Evans J, Yusuf S, AL-Nahhas A, Mauri F, Barwick T, Aboagye Eet al., 2017, 68Ga-DOTATATE PET/CT to predict response to peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumours (NETs), ASCO, Publisher: American Society of Clinical Oncology, ISSN: 0732-183X

Conference paper

Challapalli A, Carroll L, Aboagye EO, 2017, Molecular mechanisms of hypoxia in cancer, Clinical and Translational Imaging, Vol: 5, Pages: 225-253, ISSN: 2281-5872

PurposeHypoxia is a condition of insufficient oxygen to support metabolism which occurs when the vascular supply is interrupted, or when a tumour outgrows its vascular supply. It is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. This review provides an overview of hypoxia imaging with Positron emission tomography (PET), with an emphasis on the biological relevance, mechanism of action, highlighting advantages, and limitations of the currently available hypoxia radiotracers.MethodsA comprehensive PubMed literature search was performed, identifying articles relating to biological significance and measurement of hypoxia, MRI methods, and PET imaging of hypoxia in preclinical and clinical settings, up to December 2016.ResultsA variety of approaches have been explored over the years for detecting and monitoring changes in tumour hypoxia, including regional measurements with oxygen electrodes placed under CT guidance, MRI methods that measure either oxygenation or lactate production consequent to hypoxia, different nuclear medicine approaches that utilise imaging agents the accumulation of which is inversely related to oxygen tension, and optical methods. The advantages and disadvantages of these approaches are reviewed, along with individual strategies for validating different imaging methods. PET is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels.ConclusionEven though hypoxia could have significant prognostic and predictive value in the clinic, the best method for hypoxia assessment has in our opinion not been realised.

Journal article

Cysouw MCF, Kramer GM, Frings V, De Langen AJ, Wondergem MJ, Kenny LM, Aboagye EO, Kobe C, Wolff J, Hoekstra OS, Boellaard Ret al., 2017, Baseline and longitudinal variability of normal tissue uptake values of [F-18]-fluorothymidine-PET images, Nuclear Medicine and Biology, Vol: 51, Pages: 18-24, ISSN: 0969-8051

Purpose[18F]-fluorothymidine ([18F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution.Methods18F–FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated. Twenty-three patients received double baseline scans, and another 39 patients were also scanned early and late during systemic treatment with a tyrosine kinase inhibitor. Reproducible volume of interest were placed in blood pool, lung, liver, and bone marrow. For semi-quantitative analysis, SUVmean, SUVmax, and SUVpeak with several normalizations were derived.ResultsSUVs of basal lung, liver, and bone marrow were not significantly different between averaged dynamic and static images, in contrast with blood pool and apical lung. Highest repeatability was seen for liver and bone marrow, with repeatability coefficients of 18.6% and 20.4% when using SUVpeak. Systemic treatment with TKIs both increased and decreased normal tissue tracer uptake at early and late time points during treatment.ConclusionSimultaneous evaluation of liver and bone marrow uptake in longitudinal response studies may be used to assess image quality, where changes in uptake outside repeatability limits should trigger investigators to perform additional quality control on individual PET images.Advances in knowledgeFor [18F]-FLT PET images, liver and bone marrow have low intra-patient variability when quantified with SUVpeak, but may be affected by systemic treatment.Implications for patient careIn [18F]-FLT-PET response monitoring trials, liver and bone marrow uptake may be used for quality control of [18F]-FLT PET images

Journal article

Valindria V, Lavdas I, Bai W, Kamnitsas K, Aboagye E, Rockall A, Rueckert D, Glocker Bet al., 2017, Reverse classification accuracy: predicting segmentation performance in the absence of ground truth, IEEE Transactions on Medical Imaging, Vol: 36, Pages: 1597-1606, ISSN: 1558-254X

When integrating computational tools such as au-tomatic segmentation into clinical practice, it is of utmostimportance to be able to assess the level of accuracy on newdata, and in particular, to detect when an automatic methodfails. However, this is difficult to achieve due to absence of groundtruth. Segmentation accuracy on clinical data might be differentfrom what is found through cross-validation because validationdata is often used during incremental method development, whichcan lead to overfitting and unrealistic performance expectations.Before deployment, performance is quantified using differentmetrics, for which the predicted segmentation is compared toa reference segmentation, often obtained manually by an expert.But little is known about the real performance after deploymentwhen a reference is unavailable. In this paper, we introduce theconcept ofreverse classification accuracy(RCA) as a frameworkfor predicting the performance of a segmentation method onnew data. In RCA we take the predicted segmentation froma new image to train a reverse classifier which is evaluatedon a set of reference images with available ground truth. Thehypothesis is that if the predicted segmentation is of good quality,then the reverse classifier will perform well on at least some ofthe reference images. We validate our approach on multi-organsegmentation with different classifiers and segmentation methods.Our results indicate that it is indeed possible to predict the qualityof individual segmentations, in the absence of ground truth. Thus,RCA is ideal for integration into automatic processing pipelines inclinical routine and as part of large-scale image analysis studies.

Journal article

Schelhaas S, Heinzmann K, Bollineni V, Kramer G, Liu Y, Waterton J, Aboagye E, Shields A, Soloviev D, Jacobs Aet al., 2017, Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review, Theranostics, Vol: 7, Pages: 40-50, ISSN: 1838-7640

The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.

Journal article

Sharma R, Mapelli P, Hanna GB, Goldin R, Power D, Al-Nahhas A, Merchant S, Ramaswami R, Challapalli A, Barwick T, Aboagye EOet al., 2016, Evaluation of F-18-fluorothymidine positron emission tomography ([F-18] FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer, EJNMMI Research, Vol: 6, ISSN: 2191-219X

Background3’-Deoxy-3’-[18F]fluorothymidine ([18F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [18F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy.Dynamic [18F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [18F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1.ResultsTen patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [18F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [18F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response.ConclusionsThe results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [18F]FLT-PET/CT. However, [18F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [18F]FLT-PET/CT studies in this tumour type should be undertaken with caution.

Journal article

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

Periyasamy M, Nguyen VTM, Patel H, Lai C-F, Nevedomskaya E, Harrod A, Buluwela L, Ali Set al., 2016, Cytidine deamination activity of APOBEC3B regulates estrogen receptor function in breast cancer, UK Breast Cancer Research Symposium, Publisher: Springer Verlag (Germany), Pages: 197-197, ISSN: 1573-7217

Conference paper

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

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: id=00169625&limit=30&person=true&page=3&respub-action=search.html