Publications
112 results found
Gauthier TP, Wasan HS, Muhammad A, et al., 2011, Assessment of Global Liver Blood Flow With Quantitative Dynamic Contrast-Enhanced Ultrasound, JOURNAL OF ULTRASOUND IN MEDICINE, Vol: 30, Pages: 379-385, ISSN: 0278-4297
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- Citations: 10
Owen DRJ, Piccini P, Matthews PM, 2011, Towards molecular imaging of multiple sclerosis, MULTIPLE SCLEROSIS JOURNAL, Vol: 17, Pages: 262-272, ISSN: 1352-4585
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- Citations: 7
Owen DRJ, Lewis AJM, Reynolds R, et al., 2011, Variation in Binding Affinity of the Novel Anxiolytic XBD173 for the 18 kDa Translocator Protein in Human Brain, SYNAPSE, Vol: 65, Pages: 257-259, ISSN: 0887-4476
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- Citations: 43
Pike VW, Taliani S, Lohith TG, et al., 2011, Evaluation of novel N1-methyl-2-phenylindol-3-ylglyoxylamides as a new chemotype of 18 kDa translocator protein-selective ligand suitable for the development of positron emission tomography radioligands, J Med Chem, Vol: 54, Pages: 366-373, ISSN: 1520-4804
A novel series of N(1)-methyl-(2-phenylindol-3-yl)glyoxylamides, 19-31, designed in accordance with our previously reported pharmacophore/topological model, showed high affinity for the 18 kDa translocator protein (TSPO) and paved the way for developing a new radiolabeled probe. Thus ligand 31, N,N-di-n-propyl-(N(1)-methyl-2-(4'-nitrophenyl)indol-3-yl)glyoxylamide, featuring the best combination of affinity and lipophilicity, was labeled with carbon-11 for evaluation with positron emission tomography (PET) in monkey. After intravenous injection, [(11)C]31 entered brain to give a high proportion of TSPO-specific binding. These findings augur well for the future application of [(11)C]31 in humans. Consequently, the binding of 31 to human TSPO was tested on samples of brain membranes from deceased subjects who through ethically approved in vitro study had previously been established to be high-affinity binders (HABs), mixed-affinity binders (MABs), or low-affinity binders (LABs) for the known TSPO ligand, PBR28 (2). 31 showed high affinity for HABs, MABs, and LABs. In conclusion, [(11)C]31 represents a promising new chemotype for developing novel TSPO radioligands as biomarkers of neuroinflammation.
Owen DRJ, Lindsay AC, Choudhury RP, et al., 2011, Imaging of Atherosclerosis, ANNUAL REVIEW OF MEDICINE, VOL 62, 2011, Vol: 62, Pages: 25-40, ISSN: 0066-4219
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- Citations: 87
Owen DR, Gunn RN, Rabiner EA, et al., 2011, Mixed-affinity binding in humans with 18-kDa translocator protein ligands, J Nucl Med, Vol: 52, Pages: 24-32, ISSN: 1535-5667
11C-PBR28 PET can detect the 18-kDa translocator protein (TSPO) expressed within macrophages. However, quantitative evaluation of the signal in brain tissue from donors with multiple sclerosis (MS) shows that PBR28 binds the TSPO with high affinity (binding affinity [Ki], approximately 4 nM), low affinity (Ki, approximately 200 nM), or mixed affinity (2 sites with Ki, approximately 4 nM and approximately 300 nM). Our study tested whether similar binding behavior could be detected in brain tissue from donors with no history of neurologic disease, with TSPO-binding PET ligands other than 11C-PBR28, for TSPO present in peripheral blood, and with human brain PET data acquired in vivo with 11C-PBR28. METHODS: The affinity of TSPO ligands was measured in the human brain postmortem from donors with a history of MS (n=13), donors without any history of neurologic disease (n=20), and in platelets from healthy volunteers (n=13). Binding potential estimates from thirty-five 11C-PBR28 PET scans from an independent sample of healthy volunteers were analyzed using a gaussian mixture model. RESULTS: Three binding affinity patterns were found in brains from subjects without neurologic disease in similar proportions to those reported previously from studies of MS brains. TSPO ligands showed substantial differences in affinity between subjects classified as high-affinity binders (HABs) and low-affinity binders (LABs). Differences in affinity between HABs and LABs are approximately 50-fold with PBR28, approximately 17-fold with PBR06, and approximately 4-fold with DAA1106, DPA713, and PBR111. Where differences in affinity between HABs and LABs were low ( approximately 4-fold), distinct affinities were not resolvable in binding curves for mixed-affinity binders (MABs), which appeared to express 1 class of sites with an affinity approximately equal to the mean of those for HABs and LABs. Mixed-affinity binding was detected in platelets from an independent sample (HAB, 69%; MAB, 31%), al
Woodward H, Owen DRJ, Bicknell CD, 2011, PERI-OPERATIVE SMOKING CESSATION: LOST IN TRANSLATION?, ADVANCES IN MEDICINE AND BIOLOGY, VOL 12, Editors: Berhardt, Publisher: NOVA SCIENCE PUBLISHERS, INC, Pages: 141-147, ISBN: 978-1-61728-994-1
Owen DRJ, Matthews PM, 2011, IMAGING BRAIN MICROGLIAL ACTIVATION USING POSITRON EMISSION TOMOGRAPHY AND TRANSLOCATOR PROTEIN-SPECIFIC RADIOLIGANDS, BIOMARKERS OF NEUROLOGICAL AND PSYCHIATRIC DISEASE, Vol: 101, Pages: 19-39, ISSN: 0074-7742
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- Citations: 69
Gaemperli O, Shalhoub J, Owen D, et al., 2010, Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 11C-PK11195 PET/CT, CIRCULATION, Vol: 122, ISSN: 0009-7322
Miller S, Owen DR, Shalhoub J, et al., 2010, Late-Phase Contrast-enhanced US to Assess Unstable Carotid Atherosclerotic Plaques Response, RADIOLOGY, Vol: 257, Pages: 589-589, ISSN: 0033-8419
Pastor CM, 2010, Gadoxetic Acid-enhanced Hepatobiliary Phase MR Imaging: Cellular Insight, RADIOLOGY, Vol: 257, Pages: 589-589, ISSN: 0033-8419
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- Citations: 6
Gaemperli O, Shalhoub J, Owen D, et al., 2010, Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 PET/CT, ESC Congress, Publisher: OXFORD UNIV PRESS, Pages: 451-451, ISSN: 0195-668X
Guo Q, Owen DR, Bennacef I, et al., 2010, Predicting the in vivo performance of TSPO PET radioligands using a biomathematical modelling approach, 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S143-S143, ISSN: 1053-8119
Owen DR, Rabiner EA, Gunn RN, et al., 2010, PBR28, PBR06 and PBR111 bind two distinct TSPO sites in human brain tissue, 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S30-S31, ISSN: 1053-8119
Owen DR, Shalhoub J, Miller S, et al., 2010, Inflammation within Carotid Atherosclerotic Plaque: Assessment with Late-Phase Contrast-enhanced US, RADIOLOGY, Vol: 255, Pages: 638-644, ISSN: 0033-8419
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- Citations: 67
Abdul-Salam VB, Ramrakha P, Krishnan U, et al., 2010, Identification and Assessment of Plasma Lysozyme as a Putative Biomarker of Atherosclerosis, ARTERIOSCL THROM VAS, Vol: 30, Pages: 1027-U306, ISSN: 1079-5642
Shalhoub J, Owen DRJ, Gauthier T, et al., 2010, The use of Contrast Enhanced Ultrasound in Carotid Arterial Disease, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 39, Pages: 381-387, ISSN: 1078-5884
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- Citations: 51
Shalhoub J, Owen D, Miller S, et al., 2010, Novel late-phase contrast-enhanced ultrasound to assess carotid atherosclerotic plaques in humans, 44th Annual Scientific Meeting of the Vascular-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: 4-4, ISSN: 0007-1323
Owen DR, Howell OW, Tang SP, et al., 2010, Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation, J Cereb Blood Flow Metab, Vol: 30, Pages: 1608-1618, ISSN: 1559-7016
[(11)C]PBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for [(11)C]PK11195, another TSPO radioligand. We measured the specific binding signals with [(3)H]PK11195 and [(3)H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [(3)H]PBR28, although all samples showed [(3)H]PK11195 binding. There was a marked reduction in the affinity of [(3)H]PBR28 for TSPO in samples with no visible [(3)H]PBR28 autoradiographic signal (K(i)=188+/-15.6 nmol/L), relative to those showing normal signal (K(i)=3.4+/-0.5 nmol/L, P<0.001). Of this latter group, [(3)H]PBR28 bound with a two-site fit in 40% of cases, with affinities (K(i)) of 4.0+/-2.4 nmol/L (high-affinity site) and 313+/-77 nmol/L (low-affinity site). There was no difference in K(d) or B(max) for [(3)H]PK11195 in samples showing no [(3)H]PBR28 autoradiographic signal relative to those showing normal [(3)H]PBR28 autoradiographic signal. [(3)H]PK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in [(11)C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.
McGinty J, Dunsby C, Auksorius E, et al., 2009, Chapter 4 Multidimensional fluorescence imaging
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- Citations: 3
Owen D, Paranandi B, Sivakumar R, et al., 2007, Classical diseases revisited: transient global amnesia, POSTGRADUATE MEDICAL JOURNAL, Vol: 83, Pages: 236-239, ISSN: 0032-5473
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- Citations: 36
Mahmud M, Wade C, Jawad S, et al., A Reliable Test-Retest Measure of Positron Emission Tomographic Imaging of Translocator Protein in Temporal Lobe Epilepsy, SSRN Electronic Journal
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