332 results found
Willaime JMY, Turkheimer FE, Kenny LM, et al., 2013, Quantification of intra-tumour cell proliferation heterogeneity using imaging descriptors of 18F fluorothymidine-positron emission tomography, Physics in medicine and biology, Vol: 58, Pages: 187-203
Intra-tumour heterogeneity is a characteristic shared by all cancers. We explored the use of texture variables derived from images of [(18)F]fluorothymidine-positron emission tomography (FLT-PET), thus notionally assessing the heterogeneity of proliferation in individual tumours. Our aims were to study the range of textural feature values across tissue types, verify the repeatability of these image descriptors and further, to explore associations with clinical response to chemotherapy in breast cancer patients. The repeatability of 28 textural descriptors was assessed in patients who had two FLT-PET scans prior to therapy using relative differences and the intra-class correlation coefficient (ICC). We tested associations between features at baseline and clinical response measured in 11 patients after three cycles of chemotherapy, and explored changes in FLT-PET at one week after the start of therapy. A subset of eight features was characterized by low variations at baseline (<30%) and high repeatability (0.7 ≤ ICC ≤ 1). The intensity distribution profile suggested fewer highly proliferating cells in lesions of non-responders compared to responders at baseline. A true increase in CV and homogeneity was measured in four out of six responders one week after the start of therapy. A number of textural features derived from FLT-PET are altered following chemotherapy in breast cancer, and should be evaluated in larger clinical trials for clinical relevance.
Gallo J, Long NJ, Aboagye EO, 2013, Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer, CHEMICAL SOCIETY REVIEWS, Vol: 42, Pages: 7816-7833, ISSN: 0306-0012
Tietz O, Kamaly N, Smith G, et al., 2013, Design, synthesis and in vitro characterization of fluorescent and paramagnetic CXCR4-targeted imaging agents., Am J Nucl Med Mol Imaging, Vol: 3, Pages: 372-383, ISSN: 2160-8407
The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core, encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to the CXCR4 receptor. The particles were characterized for their size, surface charge and r2 relaxivity at 4.7 T. MR imaging of the CXCR4 receptor with targeted iron oxide nanoparticles revealed an approximately 3-fold increase in T2 signal enhancement of MDA-MB-231 cells compared to non-targeted controls. Prussian blue staining of labeled MDA-MB-231 cells revealed darker and more intense staining of the cellular membrane. This study demonstrates the potential of targeted iron oxide nanoparticles for the imaging of the CXCR4 receptor by magnetic resonance imaging (MRI).
Trousil S, Carroll L, Kalusa A, et al., 2013, Design of symmetrical and nonsymmetrical N,N-dimethylaminopyridine derivatives as highly potent choline kinase alpha inhibitors, MedChemComm, Vol: 4, Pages: 693-696, ISSN: 2040-2503
Choline kinase alpha is hyperactivated in many solid tumours and regulates malignant progression, making it a promising cancer drug target. The successful design and synthesis of novel inhibitors with high cellular activity are described.
Smith G, Carroll L, Aboagye EO, 2012, New Frontiers in the Design and Synthesis of Imaging Probes for PET Oncology: Current Challenges and Future Directions, MOLECULAR IMAGING AND BIOLOGY, Vol: 14, Pages: 653-666, ISSN: 1536-1632
Perumal M, Stronach EA, Gabra H, et al., 2012, Evaluation of 2-Deoxy-2-[F-18]Fluoro-D-glucose- and 3 '-Deoxy-3 '-[F-18]Fluorothymidine-Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer, MOLECULAR IMAGING AND BIOLOGY, Vol: 14, Pages: 753-761, ISSN: 1536-1632
Tomasi G, Shepherd T, Turkheimer F, et al., 2012, Comparative assessment of segmentation algorithms for tumor delineation on a test-retest [C-11]choline dataset, MEDICAL PHYSICS, Vol: 39, Pages: 7571-7579, ISSN: 0094-2405
Trousil S, Kaliszczak M, Carroll L, et al., 2012, ICL-CCIC-0019, a Novel and Selective Inhibitor of Choline Kinase Alpha with Significant Antitumor Activity, 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 56-56, ISSN: 0959-8049
Kaliszczak M, Trousil S, Aberg O, et al., 2012, HDAC6 Inhibitor C1A Synergizes with BEZ-235 in Colon Cancer Cells in Vitro and Potently Inhibits Tumor Growth in Vivo, 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 162-162, ISSN: 0959-8049
Fortt R, Smith G, Awais RO, et al., 2012, Automated GMP Synthesis of [F-18]ICMT-11 for In Vivo Imaging of Caspase-3 Activity, NUCLEAR MEDICINE AND BIOLOGY, Vol: 39, Pages: 1000-1005, ISSN: 0969-8051
Carroll L, Perumal M, Vasdev N, et al., 2012, Radiosynthesis and in vivo tumor uptake of 2-deoxy-2-[F-18]fluoro-myo-inositol, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, Vol: 22, Pages: 6148-6150, ISSN: 0960-894X
Sharma R, Kallur KG, Ryu JS, et al., 2012, Test-retest reproducibility of [F-18]fluciclatide PET imaging in subjects with solid tumors, 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S226-S226, ISSN: 1619-7070
Lake MC, Quang-De N, Ali S, et al., 2012, Development of a Novel Molecular Sensor for Imaging Estrogen Receptor-Coactivator Protein-Protein Interactions, PLOS ONE, Vol: 7, ISSN: 1932-6203
Smith G, Sala R, Carroll L, et al., 2012, Synthesis and evaluation of nucleoside radiotracers for imaging proliferation, NUCLEAR MEDICINE AND BIOLOGY, Vol: 39, Pages: 652-665, ISSN: 0969-8051
Aboagye EO, Gilbert FJ, Fleming IN, et al., 2012, Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials, EUROPEAN RADIOLOGY, Vol: 22, Pages: 1465-1478, ISSN: 0938-7994
Contractor K, Challapalli A, Tomasi G, et al., 2012, Imaging of cellular proliferation in liver metastasis by [F-18]fluorothymidine positron emission tomography: effect of therapy, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 57, Pages: 3419-3433, ISSN: 0031-9155
Tomasi G, Kimberley S, Rosso L, et al., 2012, Double-input compartmental modeling and spectral analysis for the quantification of positron emission tomography data in oncology, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 57, Pages: 1889-1906, ISSN: 0031-9155
Tomasi G, Turkheimer F, Aboagye E, 2012, Importance of Quantification for the Analysis of PET Data in Oncology: Review of Current Methods and Trends for the Future, MOLECULAR IMAGING AND BIOLOGY, Vol: 14, Pages: 131-146, ISSN: 1536-1632
Contractor K, Aboagye EO, Jacob J, et al., 2012, Monitoring early response to taxane therapy in advanced breast cancer with circulating tumor cells and [F-18] 3 '-deoxy-3 '-fluorothymidine PET: a pilot study, BIOMARKERS IN MEDICINE, Vol: 6, Pages: 231-233, ISSN: 1752-0363
Quang-De N, Challapalli A, Smith G, et al., 2012, Imaging apoptosis with positron emission tomography: 'Bench to bedside' development of the caspase-3/7 specific radiotracer [F-18]ICMT-11, EUROPEAN JOURNAL OF CANCER, Vol: 48, Pages: 432-440, ISSN: 0959-8049
Aberg O, Pisaneschi F, Smith G, et al., 2012, F-18-labelling of a cyclic pentapeptide inhibitor of the chemokine receptor CXCR4, JOURNAL OF FLUORINE CHEMISTRY, Vol: 135, Pages: 200-206, ISSN: 0022-1139
Soloviev D, Lewis D, Honess D, et al., 2012, [(18)F]FLT: an imaging biomarker of tumour proliferation for assessment of tumour response to treatment., Eur J Cancer, Vol: 48, Pages: 416-424
The paradigm of drug development is shifting towards early use of imaging biomarkers as surrogate end-points in clinical trials. Quantitative Imaging in Cancer: Connecting Cellular Processes (QuIC-ConCePT) is an initiative to qualify complementary imaging biomarkers (IB) of proliferation, cell death and tumour heterogeneity as possible tools in early phase clinical trials to help pharmaceutical developers in 'go, no-go' decisions early in the process of drug development. One of the IBs is [(18)F]3'-deoxy-3'-fluorothymidine with Positron Emission Tomography (FLT-PET). We review results of recent clinical trials using FLT-PET for monitoring tumour response to drug treatment and discuss the potential and the possible pitfalls of using this IB as a surrogate end-point in early phase clinical trials for assessing tumour response to drug treatment. From first human trial results it seems that the degree of FLT accumulation in tumours is governed not only by the tumour proliferation rate but also by other factors. Nevertheless FLT-PET could potentially be used as a negative predictor of tumour response to chemotherapy, and hence evaluation of this IB is granted in multi-centre clinical trials.
Witney TH, Alam IS, Turton DR, et al., 2012, Evaluation of Deuterated F-18- and C-11-Labeled Choline Analogs for Cancer Detection by Positron Emission Tomography, CLINICAL CANCER RESEARCH, Vol: 18, Pages: 1063-1072, ISSN: 1078-0432
Evans HL, Slade RL, Carroll L, et al., 2012, Copper-free click-a promising tool for pre-targeted PET imaging, CHEMICAL COMMUNICATIONS, Vol: 48, Pages: 991-993, ISSN: 1359-7345
Vengadabady L, Thielemans K, McCabe D, et al., 2012, Comparing respiratory and patient movement during dynamic PET, 2012 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD (NSS/MIC), Pages: 4005-4008, ISSN: 1095-7863
Contractor KB, Kenny LM, Coombes CR, et al., 2012, Evaluation of limited blood sampling population input approaches for kinetic quantification of [F-18]fluorothymidine PET data, EJNMMI RESEARCH, Vol: 2, ISSN: 2191-219X
Aboagye EO, Smith G, Robins EG, et al., 2012, WO2012/040133: Novel precursor. [Deuterated fluorocholine precursor]
Aboagye EO, Robins EG, Smith G, et al., 2012, WO2012/040138: Novel radiotracer. [Deuterated fluorocholine imaging agent]
Aboagye EO, Robins EG, Smith G, et al., 2012, WO2012/040151: Isotopic carbon choline analogues. [Deuterated choline imaging agent]
Aboagye EO, Kaliszczak M, 2012, WO2012/175973: Combination treatment comprising a HDAC6 inhibitor and and AKT inhibitor
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