Vincent J Cunningham
Affiliation: GlaxoSmithKline Research and Development
- Measuring drug occupancy in the absence of a reference region: the Lassen plot re-visitedVincent J Cunningham
GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London, UK
J Cereb Blood Flow Metab 30:46-50. 2010..We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of V(T) alone to determine occupancy, together with an extension that does not require baseline data...
- PET studies in drug development: Methodological considerationsVincent J Cunningham
Translational Medicine and Genetics, GlaxoSmithKline, 891 995 Greenford Road, Greenford, Middlesex, UK UB6 7HE Electronic
Drug Discov Today Technol 2:311-5. 2005....
- Evaluation of 11C-GSK189254 as a novel radioligand for the H3 receptor in humans using PETSharon Ashworth
GlaxoSmithKline Clinical Imaging Centre, Imperial College London, Hammersmith Hospital, London, United Kingdom
J Nucl Med 51:1021-9. 2010..The purpose of the present study was to evaluate (11)C-GSK189254 as a PET radioligand for human studies and to determine the dose-receptor occupancy relationship of GSK189254 in the human brain...
- A bolus/infusion paradigm for the novel NMDA receptor SPET tracer [123I]CNS 1261Rodrigo A Bressan
Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK
Nucl Med Biol 31:155-64. 2004..Good agreement was obtained between kinetic and equilibrium analysis. SPET scanning with a bolus-infusion protocol is a valid method to estimate the total volume of distribution for [(123)I]CNS 1261 in clinical populations...
- Validation of a tracer kinetic model for the quantification of 5-HT(2A) receptors in human brain with [(11)C]MDL 100,907Rainer Hinz
Hammersmith Imanet Ltd, London, UK
J Cereb Blood Flow Metab 27:161-72. 2007..This study confirmed the use of an arterial input kinetic model for the quantification of 5-HT(2A) receptor binding with [(11)C]MDL 100,907 and the use of the cerebellum as a reference region for the free and nonspecific binding...
- Radiosynthesis and characterization of 11C-GSK215083 as a PET radioligand for the 5-HT6 receptorChristine A Parker
Clinical Imaging Centre, GlaxoSmithKline, London, UK
J Nucl Med 53:295-303. 2012..In addition, such a tool would assist in the development of novel drugs targeting the 5-HT6 receptor...
- Human Kinetic Modeling of the 5HT6 PET Radioligand 11C-GSK215083 and Its Utility for Determining Occupancy at Both 5HT6 and 5HT2A Receptors by SB742457 as a Potential Therapeutic Mechanism of Action in Alzheimer DiseaseChristine A Parker
GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London, United Kingdom Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom
J Nucl Med 56:1901-9. 2015....
- 11C-GSK189254: a selective radioligand for in vivo central nervous system imaging of histamine H3 receptors by PETChristophe Plisson
GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London, United Kingdom
J Nucl Med 50:2064-72. 2009..The aim of this study was to synthesize and evaluate (11)C-labeled GSK189254 ((11)C-GSK189254) for imaging the histamine H(3) receptor in vivo by PET...
- A pharmacokinetic PET study of NK₁ receptor occupancyStefano Zamuner
GlaxoSmithKline, Clinical Pharmacology Modeling and Simulation, Stockley Park, UK
Eur J Nucl Med Mol Imaging 39:226-35. 2012..Here we present a study in human subjects of the occupancy of NK(1) receptors achieved following different doses of casopitant, a selective NK(1) antagonist...
- Non linear mixed effects analysis in PET PK-receptor occupancy studiesAlienor Berges
GlaxoSmithKline, Clinical Pharmacology Modelling and Simulation, Stockley Park, UK
Neuroimage 76:155-66. 2013..6% and 689.5% from NLLS). Overall, the NLME approach provided a more robust estimation and produced less-biassed estimates of the population means and variances than either the NLLS approach for the simulations considered...
- On the logic of hypothesis testing in functional imagingFederico E Turkheimer
Department of Neuropathology, Imperial College London, Charing Cross Hospital, St Dunstan s Road, London, W6 8RP, UK
Eur J Nucl Med Mol Imaging 31:725-32. 2004..The (smaller) set of likely spatial patterns generated is then tested with newer data and a more rigorous multiple hypothesis testing technique (deductive step)...
- Characterization of the SPECT 5-HT2A receptor ligand 123I-R91150 in healthy volunteers: Part 1--pseudoequilibrium interval and quantification methodsAna M Catafau
Experimental Medical Sciences, Clinical Pharmacology Discovery Medicine, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Barcelona, Spain
J Nucl Med 47:919-28. 2006..The pseudoequilibrium interval after a single bolus injection was identified, and a reference database of specific uptake ratio (SUR) values was obtained. Within-scan and between-subject variability was also assessed...
- Behaviour of [11C]R(-)- and [11C]S(+)-rolipram in vitro and in vivo, and their use as PET radiotracers for the quantificative assay of PDE4Christine A Parker
GlaxoSmithKline, ACCI Addenbrooke s Hospital, Hills Road, Cambridge, CB2 2GG, UK
Synapse 55:270-9. 2005..7 from the in vivo studies using [(11)C]S(+)-rolipram. To conclude, the in vitro affinities of R(-)- and S(+)-rolipram predict their apparent in vivo behaviour in the porcine brain, as measured by PET...
- Rank-shaping regularization of exponential spectral analysis for application to functional parametric mappingFederico E Turkheimer
Hammersmith Imanet, Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Phys Med Biol 48:3819-41. 2003..Through application to simulated and real datasets, it is shown that RS ameliorates and extends SA properties in the case of the production of functional parametric maps from PET studies...
- Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trialsEric O Aboagye
Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, MRC Cyclotron Building, Hammersmith Hospital Campus, London, W12 0NN, UK
Eur Radiol 22:1465-78. 2012....
- A multi-center randomized proof-of-concept clinical trial applying [¹⁸F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer's diseaseSofia Tzimopoulou
GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, London, UK
J Alzheimers Dis 22:1241-56. 2010..It suggests that Rosiglitazone is associated with an early increase in whole brain glucose metabolism, but not with any biological or clinical evidence for slowing progression over a 1 year follow up in the symptomatic stages of AD...
- Prediction of repeat-dose occupancy from single-dose data: characterisation of the relationship between plasma pharmacokinetics and brain target occupancySergio Abanades
GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London, UK
J Cereb Blood Flow Metab 31:944-52. 2011..29±1.11 ng/mL). This approach increases the value of SD occupancy studies that are performed as part of first time in human drug development programmes by providing an estimate of the dose required to achieve the desired TO at RD...
- Analysis of D2 dopamine receptor occupancy with quantitative SPET using the high-affinity ligand [123I]epidepride: resolving conflicting findingsKjell Erlandsson
Institute of Nuclear Medicine, Royal Free and University College Medical School, University College London, London, UK
Neuroimage 19:1205-14. 2003....
- On the undecidability among kinetic models: from model selection to model averagingFederico E Turkheimer
Imaging Research Solutions Ltd, Cyclotron Building, Hammersmith Hospital, London, United Kingdom
J Cereb Blood Flow Metab 23:490-8. 2003..The new method is illustrated and epitomized by a case example on the modeling of [11C]flumazenil kinetics in the brain, containing both real and simulated data...
- A linear wavelet filter for parametric imaging with dynamic PETFederico E Turkheimer
IRSL, Cyclotron Building, Hammersmith Hospital, DuCane Road, London W12 0NN, UK
IEEE Trans Med Imaging 22:289-301. 2003..Finally, the formal framework is interpreted for the practitioner's point of view and advantages and limitations of the method are discussed...