351 results found
Smith G, Carroll L, Sala R, et al., 2011, Synthesis and evaluation of nucleoside radiotracers for imaging tumour proliferation, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol: 54, Pages: S214-S214, ISSN: 0362-4803
Smith G, Zhao Y, Leyton J, et al., 2011, Radiosynthesis and pre-clinical evaluation of [F-18]fluoro-[1,2-H-2(4)]choline, NUCLEAR MEDICINE AND BIOLOGY, Vol: 38, Pages: 39-51, ISSN: 0969-8051
Contractor KB, Challapalli A, Barwick T, et al., 2011, Use of [11C]choline PET-CT as a non invasive method for detecting pelvic lymph node status from prostate cancer and relationship with choline kinase expression, ISSN: 1078-0432
PURPOSE: To evaluate the accuracy and biological basis for [11C] choline-PET-CT in the nodal staging of high risk localised prostate cancer patients.EXPERIMENTAL DESIGN: Twenty eight patients underwent dynamic [11C] choline-PET-CT of the pelvis and lower abdomen prior to extended laparoscopic pelvic lymph node dissection (eLPL). The sensitivity and specificity of [11C]choline PET, [11C]choline PET-CT and MRI for nodal detection were calculated. Average and maximal standardized Uptake Values (SUVave, SUVmax) were compared with choline kinase alpha (CHKalpha) and Ki67 immunohistochemistry scores.RESULTS: 406 lymph nodes, in 26 patients, were assessable. 27 (6.7%) involved pelvic nodes at eLPL were detected in 9 patients. 17 out of the 27 involved nodes were sub-centimetre. The sensitivity and specificity on a per nodal basis were 18.5 % and 98.7%, 40.7% and 98.4 %, and 51.9% and 98.4% for MRI, [11C]choline PET and [11C]choline PET-CT, respectively. Sensitivity was higher for [11C]choline PET-CT compared with MRI (p=0.007). A higher nodal detection rate, including sub-centimetre nodes, was seen with [11C]choline PET-CT than MRI. Malignant lesions showed CHKalpha expression in both cytoplasm and nucleus. SUVave and SUVmax strongly correlated with CHKalpha staining intensity (r=0.68, p<0.0001 and r=0.63, p=0.0004, respectively). In contrast, Ki67 expression was generally low in all tumors. CONCLUSIONS: This study establishes the relationship between [11C]choline PET- CT uptake with choline kinase expression in prostate cancer and allows it to be used as a non-invasive means of staging pelvic lymph nodes, being highly specific and more sensitive than MRI including the detection of sub-centimetre disease.
Contractor KB, Kenny LM, Stebbing J, et al., 2011, Biological basis of [11C]choline-positron emission tomography in patients with breast cancer: comparison with [18F]fluorothymidine positron emission tomography, ISSN: 1473-5628
OBJECTIVE: The biological significance of [C]choline (CHO) uptake in human tumours is unclear and probably linked to choline kinase-alpha (CHKalpha) expression and cell proliferation. We directly compared CHO with [F]fluorothymidine (FLT), an imaging biomarker of proliferation, by positron emission tomography (PET) in patients with breast cancer to investigate whether cell proliferation is an important determinant of CHO uptake. Furthermore, we evaluated CHKalpha and the Ki67-labelling index (LIKi67) in tumour biopsies. METHODS: Sequential CHO-PET and FLT-PET within the same imaging session were performed in 21 patients with oestrogen receptor (ER)-positive breast cancer (28 lesions). Average and maximum CHO standardized uptake values (SUV) at 60 min: SUV60,av, and SUV60,max, and the rate constant of net irreversible uptake, Ki, were compared with FLT uptake at 60 min: SUV60,av and SUV60,max. Biopsies were stained for CHKalpha and LIKi67 in eight cases. RESULTS: Tumours were equally visible on CHO-PET and FLT-PET imaging. Tumour CHO-PET strongly correlated with FLT imaging variables (Pearson's r=0.83; P<0.0001 for CHO-SUV60,max vs. FLT-SUV60,max). A statistically significant association was found between CHO-PET variables and categorical scores of cytoplasmic CHKalpha intensity and between FLT-PET and LIKi67 (P<0.05, one-way analysis of variance). CONCLUSION: Choline metabolism and proliferation as assessed by PET were correlated in ER-positive breast cancer, indicating that high CHO uptake is a measure of cellular proliferation in this setting. CHO uptake was also found to be related to cytoplasmic CHKalpha expression.
Contractor KB, Kenny L, Stebbing J, et al., 2011, [18F]-3'deoxy-3'-Fluorothymidine Positron Emission Tomography and Breast Cancer Response to Docetaxel, ISSN: 1078-0432
PURPOSE: To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [18F]-3'deoxy-3'-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer.EXPERIMENTAL DESIGN: This was a prospective unblinded study in 20 patients with AJCC stage II-IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan two weeks after initiating the first or second cycle of docetaxel. PET variables were compared to anatomical response mid-therapy (after 3 cycles). RESULTS: Average and maximum tumor standardized uptake values at 60 min (SUV60,av and SUV60,max) normalized to body surface area ranged between 1.7 and 17.0, and 5.6 and 26.9 x 10-5 m2/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (p=0.0003 for SUV60,av and p=0.0002 for SUV60,max). Reduction in tumor SUV60,av was associated with target lesion size changes mid-therapy (Pearson R for SUV60,av=0.64; p=0.004) and predicted mid-therapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV60,av in responders were due at least in part, to reduced net intracellular trapping of FLT (rate constant Ki). Docetaxel significantly reduced Ki by 51.1% (+/-28.4%, p=0.0009).CONCLUSIONS: Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response mid-therapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non-FLT-PET response.
Aboagye EO, 2010, The future of imaging: developing the tools for monitoring response to therapy in oncology: the 2009 Sir James MacKenzie Davidson Memorial lecture, BRITISH JOURNAL OF RADIOLOGY, Vol: 83, Pages: 814-822, ISSN: 0007-1285
Pisaneschi F, Nguyen Q-D, Shamsaei E, et al., 2010, Development of a new epidermal growth factor receptor positron emission tomography imaging agent based on the 3-cyanoquinoline core: Synthesis and biological evaluation, BIOORGANIC & MEDICINAL CHEMISTRY, Vol: 18, Pages: 6634-6645, ISSN: 0968-0896
Hatt M, Rest CC-L, Aboagye EO, et al., 2010, Reproducibility of F-18-FDG and 3 '-Deoxy-3 '-F-18-Fluorothymidine PET Tumor Volume Measurements, JOURNAL OF NUCLEAR MEDICINE, Vol: 51, Pages: 1368-1376, ISSN: 0161-5505
Kenny LM, Contractor KB, Hinz R, et al., 2010, Reproducibility of [C-11]Choline-Positron Emission Tomography and Effect of Trastuzumab, CLINICAL CANCER RESEARCH, Vol: 16, Pages: 4236-4245, ISSN: 1078-0432
Aboagye EO, 2010, Phosphatidylcholine Metabolic Transformation and Progression Signature as a Pharmacodynamic Biomarker, ONCOTARGET, Vol: 1, Pages: 163-166
Aboagye EO, 2010, Phosphatidylcholine metabolic transformation and progression signature as a pharmacodynamic biomarker., Oncotarget, Vol: 1, Pages: 163-166
Workman P, Aboagye EO, Balkwill F, et al., 2010, Guidelines for the welfare and use of animals in cancer research, BRITISH JOURNAL OF CANCER, Vol: 102, Pages: 1555-1577, ISSN: 0007-0920
Akiyoshi T, Heathcote DA, Azzi J, et al., 2010, The Role of SPI6 in the Survival of Allograft Derived Dendritic Cells and Tolerance., AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 10, Pages: 561-561, ISSN: 1600-6135
Gray KR, Contractor KB, Kenny LM, et al., 2010, Kinetic filtering of [F-18]Fluorothymidine in positron emission tomography studies, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 55, Pages: 695-709, ISSN: 0031-9155
Nguyen Q-D, Aboagye EO, 2010, Imaging the life and death of tumors in living subjects: Preclinical PET imaging of proliferation and apoptosis, INTEGRATIVE BIOLOGY, Vol: 2, Pages: 483-495, ISSN: 1757-9694
Heathcote DA, Patel H, Kroll SH, et al., 2010, A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration, J Med Chem, Vol: 53, Pages: 8508-8522
Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene expression. Abnormalities in CDK activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Here, we report the identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC= 3, 30, 30, 250, and 90 nmol/L, respectively). Cell-based studies showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G/M phases. Consistent with these findings, 4k demonstrated potent antiproliferative activity in 60 cancer cell lines tested (mean GI= 280 nmol/L). Pharmacokinetic studies showed that 4k is orally bioavailable, with an elimination half-life of 178 min following oral dosing in mice. When administered at a concentration of 25 mg/kg orally, 4k inhibited human tumor xenografts and suppressed CDK substrate phosphorylation. These findings identify 4k as a novel, potent CDK selective inhibitor with potential for oral delivery in cancer patients.
Aboagye EO, Spivey A, Pisaneschi F, 2010, WO2010GB02325: Quinoline derivatives used as PET imaging agents
Aboagye EO, Smith G, Nguyen QD, et al., 2010, WO2010/026388: Isatin derivatives for use as in vivo imaging agents
Aboagye EO, Aboagye EO, Smith G, 2010, WO2010/023457: Nucleoside analogues useful as positron emission tomography (PET) imaging agents
Aboagye EO, Vigushin DM, 2010, US2010/0063144: Compounds and uses thereof [HDAC inhibitors]
Kenny LM, Contractor K, Stebbing J, et al., 2009, Changes in [F-18]Fluorothymidine Pharmacokinetics Following Capecitabine Treatment in Human Breast Cancer Detected by Positron Emission Tomography, 32nd Annual San Antonio Breast Cancer Symposium, Publisher: AMER ASSOC CANCER RESEARCH, Pages: 765S-765S, ISSN: 0008-5472
Quang-De N, Smith G, Glaser M, et al., 2009, Assessment of tumor response to therapy with the caspase-317 specific [18F]CMT-11 PET imaging tracer, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 1535-7163
Pardo OE, Latigo J, Jeffery RE, et al., 2009, The Fibroblast Growth Factor Receptor Inhibitor PD173074 Blocks Small Cell Lung Cancer Growth In vitro and In vivo, CANCER RESEARCH, Vol: 69, Pages: 8645-8651, ISSN: 0008-5472
Tennant DA, Frezza C, MacKenzie ED, et al., 2009, Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death, ONCOGENE, Vol: 28, Pages: 4009-4021, ISSN: 0950-9232
Smith G, Nguyen Q-D, Aboagye EO, 2009, Translational Imaging of Apoptosis, ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, Vol: 9, Pages: 958-967, ISSN: 1871-5206
Kenny LM, Contractor KB, Stebbing J, et al., 2009, Altered Tissue 3 '-Deoxy-3 '-[F-18]Fluorothymidine Pharmacokinetics in Human Breast Cancer following Capecitabine Treatment Detected by Positron Emission Tomography, CLINICAL CANCER RESEARCH, Vol: 15, Pages: 6649-6657, ISSN: 1078-0432
Nguyen Q-D, Smith G, Glaser M, et al., 2009, Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [F-18]-labeled isatin sulfonamide, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 16375-16380, ISSN: 0027-8424
Contractor KB, Kenny LM, Stebbing J, et al., 2009, [C-11]Choline Positron Emission Tomography in Estrogen Receptor-Positive Breast Cancer, CLINICAL CANCER RESEARCH, Vol: 15, Pages: 5503-5510, ISSN: 1078-0432
Seckl MJ, Pardo OE, Aboagye EO, et al., 2009, The FGF receptor (FGFR) inhibitor PD0173074 blocks SCLC growth in vitro and in vivo, JOURNAL OF THORACIC ONCOLOGY, Vol: 4, Pages: S385-S385, ISSN: 1556-0864
Rosso L, Gray KR, Contractor KB, et al., 2009, New Method for Segmentation of Tumors from [18F] FLT PET Images using Predefined Kinetic Classes, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 36, Pages: S193-S193, ISSN: 1619-7070
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