351 results found
Carroll L, Evans HL, Aboagye EO, et al., 2013, Bioorthogonal chemistry for pre-targeted molecular imaging - progress and prospects, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 11, Pages: 5772-5781, ISSN: 1477-0520
Challapalli A, Kenny LM, Hallett WA, et al., 2013, F-18-ICMT-11, a Caspase-3-Specific PET Tracer for Apoptosis: Biodistribution and Radiation Dosimetry, JOURNAL OF NUCLEAR MEDICINE, Vol: 54, Pages: 1551-1556, ISSN: 0161-5505
Dart DA, Waxman J, Aboagye EO, et al., 2013, Visualising Androgen Receptor Activity in Male and Female Mice, PLOS One, Vol: 8, ISSN: 1932-6203
Androgens, required for normal development and fertility of males and females, have vital roles in the reproductivetract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), aligand-dependent transcription factor. To assay and localise AR activity in vivo we generated the transgenic “ARELuc”mouse, expressing a luciferase reporter gene under the control of activated endogenous AR. In vivo imaging ofandrogen-mediated luciferase activity revealed several strongly expressing tissues in the male mouse as expectedand also in certain female tissues. In males the testes, prostate, seminal vesicles and bone marrow all showed highAR activity. In females, strong activity was seen in the ovaries, uterus, omentum tissue and mammary glands. In bothsexes AR expression and activity was also found in salivary glands, the eye (and associated glands), adipose tissue,spleen and, notably, regions of the brain. Luciferase protein expression was found in the same cell layers asandrogen receptor expression. Additionally, mouse AR expression and activity correlated well with AR expression inhuman tissues. The anti-androgen bicalutamide reduced luciferase signal in all tissues. Our model demonstrates thatandrogens can act in these tissues directly via AR, rather than exclusively via androgen aromatisation to estrogensand activation of the estrogen receptor. Additionally, it visually demonstrates the fundamental importance of ARsignalling outside the normal role in the reproductive organs. This model represents an important tool forphysiological and developmental analysis of androgen signalling, and for characterization of known and novelandrogenic or antiandrogenic compounds.
Tomasi G, Aboagye EO, 2013, Introduction to the analysis of PET data in oncology, JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS, Vol: 40, Pages: 419-436, ISSN: 1567-567X
George GPC, Pisaneschi F, Stevens E, et al., 2013, Scavenging strategy for specific activity improvement: application to a new CXCR4-specific cyclopentapeptide positron emission tomography tracer, J. Label Compd. Radiopharm.
Huisgen cycloaddition is attractive to label peptide because of its rapidity and bioorthogonality. However, for larger tracers, the physico-chemical differences between the precursor and the tracer are usually insufficient to allow their separation by HPLC, reducing the specific activity. This is of importance for peptidic tracers because the combination of their high-affinity receptor with low specific activity results in the precursor saturating the receptors, causing non-specific tracer binding. Here, we report a fast, one-pot, general strategy to circumvent this issue, yielding a tracer of improved specific activity. It consists in adding a lipophilic azide after the labeling step to scavenge unreacted precursor into a more lipophilic species that does not co-elute with the tracer. We applied this strategy to a new fluorinated cyclopentapeptidic CXCR4 antagonist for the PET imaging of cancer, CCIC15, for which we managed to reduce the apparent peptide concentration by a factor of 34 in 10 min. This tracer was radiolabeled by click chemistry with 2-[18F]fluoroethylazide, yielding the tracer in 18 ±6% (n = 5) end-of-synthesis radiochemical yields (EOS-RCY) in 1.5 h from [18F]fluoride with a specific activity of 19.4 GBq μmol 1. Preliminary biological evaluation of the probe confirmed potency and specificity for CXCR4; further biological evaluation is underway.
Nguyen QD, Lavdas I, Gubbins J, et al., 2013, Temporal and Spatial Evolution of Therapy-Induced Tumor Apoptosis Detected by Caspase-3-Selective Molecular Imaging, Clinical Cancer Research, Vol: 19, Pages: 3914-3924
Zhao L, Ashek A, Wang L, et al., 2013, Heterogeneity in lung 18FDG uptake in PAH: potential of dynamic 18FDG-PET with kinetic analysis as a bridging biomarker for pulmonary remodeling targeted treatments, Circulation
George GPC, Stevens E, Pisaneschi F, et al., 2013, Synthesis, radiolabelling and biological evaluation of new PET probes for CXCR4-specific imaging, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol: 56, Pages: S409-S409, ISSN: 0362-4803
Evans HL, Carroll L, Nguyen Q-D, et al., 2013, Copper-free 'click' chemistry as a potential pre-targeting tool for PET imaging, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol: 56, Pages: S204-S204, ISSN: 0362-4803
Sala R, Quang-De N, Patel C, et al., 2013, Regulation of 18F-fluorothymidine uptake by thymidine kinase 1 protein phosphorylation., 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Carroll L, Witney TH, Aboagye EO, 2013, Design and synthesis of novel F-18-radiolabelled glucosamine derivatives for cancer imaging, MEDCHEMCOMM, Vol: 4, Pages: 653-656, ISSN: 2040-2503
Coombes RC, Tat T, Miller ML, et al., 2013, An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study), ANNALS OF ONCOLOGY, Vol: 24, Pages: 924-930, ISSN: 0923-7534
Kaliszczak M, Trousil S, Aberg O, et al., 2013, A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth, BRITISH JOURNAL OF CANCER, Vol: 108, Pages: 342-350, ISSN: 0007-0920
Witney TH, Chandrashekran A, Fortt R, et al., 2013, Noninvasive imaging of tumor apoptosis in NSCLC with F-18-ICMT-11 positron emission tomography, AACR/SNMMI Joint Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy, Publisher: SOC NUCLEAR MEDICINE INC, Pages: 27-27, ISSN: 0161-5505
Nguyen Q, Challapalli A, Smith G, et al., 2013, Imaging apoptosis with positron emission tomography: bench-to-bedside development of the caspase-3/7-specific radiotracer [F-18] ICMT-11, AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy, Publisher: SOC NUCLEAR MEDICINE INC, Pages: 19-19, ISSN: 0161-5505
Witney TH, Carroll LS, Alam IS, et al., 2013, Noninvasive imaging of tumor glycogen storage by F-18-NFTG positron emission tomography, AACR/SNMMI Joint Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy, Publisher: SOC NUCLEAR MEDICINE INC, Pages: 27-27, ISSN: 0161-5505
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
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.
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).
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
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
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
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
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
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
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, Pages: 1-9, ISSN: 1932-6203
Anti-estrogens, in particular tissue selective anti-estrogens, have been the bedrock of adjuvant therapy for patients with estrogen receptor alpha (ERα) positive breast cancer. Though current therapies have greatly enhanced patient prognosis, there continues to be an impetus for the development of improved anti-estrogens. ERα is a nuclear receptor transcription factor which activates gene expression through the recruitment of transcriptional coactivator proteins. The SRC family of coactivators, which includes AIB1, has been shown to be of particular importance for ERα mediated transcription. ERα-AIB1 interactions are indicative of gene expression and are inhibited by anti-estrogen treatment. We have exploited the interaction between ERα and AIB1 as a novel method for imaging ERα activity using a split luciferase molecular sensor. By producing a range of ERα ligand binding domain (ER-LBD) and AIB1 nuclear receptor interacting domain (AIB-RID) N- and C-terminal firefly luciferase fragment fusion proteins, constructs which exhibited more than a 10-fold increase in luciferase activity with E2 stimulation were identified. The specificity of the E2-stimulated luciferase activity to ERα-AIB1 interaction was validated through Y537S and L539/540A ER-LBD fusion protein mutants. The primed nature of the split luciferase assay allowed changes in ERα activity, with respect to the protein-protein interactions preceding transcription, to be assessed soon after drug treatment. The novel assay split luciferase detailed in this report enabled modulation of ERα activity to be sensitively imaged in vitro and in living subjects and potentially holds much promise for imaging the efficacy of novel ERα specific therapies.
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