Development of Quantitative PET Imaging Probes for Neuroinflammation
Lead Research Organisation:
King's College London
Department Name: Neuroimaging
Abstract
Inflammation is a protective attempt by the immune response of the organism to remove the injurious stimuli as well as to initiate the healing process for the tissue. The inflammatory process is generally beneficial but an inflammation that runs unchecked can also lead to a host of diseases, such as hay fever, atherosclerosis, and rheumatoid arthritis. It is for this reason that inflammation is normally closely regulated by the body.
The brain and spinal cord are considered ?immune privileged? tissues in that they are separated from the rest of the body by a series of endothelial cells known as the blood-brain barrier, which prevent most infections from reaching the vulnerable nervous tissue. For this reason, inflammation in the CNS (Neuroinflammation) is mediated by a unique cell type, microglia. Microglia are part of the non-neuronal part of the cell population in the brain called glia, the other glial cell being the astrocytes and the oligodendrocytes. Quiescent microglia have a ramified morphology as they are constantly moving and analyzing the CNS for damaged neurons, plaques, and infectious agents; whenever an anomaly is detected, microglia enter an active state and undergo several morphological changes including the thickening and retraction of branches, the expression of immunomolecules, the secretion of cytotoxic factors, recruitment molecules and pro-inflammatory signaling molecules.
Microglial activation is therefore present early in any pathological state of the brain and the in-vivo detection of microglial activation is a key diagnostic aim. Besides, microglia chronic activation has also been suggested as a key factor in the inception and/or progression of neurodegenerative diseases like Alzheimer?s disease and Parkinson?s disease. This project aims at delivering an optimal imaging biomarker for microglia using Positron Emission Tomography (PET) technology. PET is a Nuclear Medicine modality that is able to image the distribution of radioactive labelled compounds. The interest in imaging microglia with PET radiotracers is such that more than 50 radiotracers targeting microglia are now proposed world-wide. In the context of this training proposal, we will test the most promising PET microglia tracers, devise appropriate data-processing procedures and metrics that will allow the selection of the optimal marker to be used in the future in diagnostics, research and drug development.
The brain and spinal cord are considered ?immune privileged? tissues in that they are separated from the rest of the body by a series of endothelial cells known as the blood-brain barrier, which prevent most infections from reaching the vulnerable nervous tissue. For this reason, inflammation in the CNS (Neuroinflammation) is mediated by a unique cell type, microglia. Microglia are part of the non-neuronal part of the cell population in the brain called glia, the other glial cell being the astrocytes and the oligodendrocytes. Quiescent microglia have a ramified morphology as they are constantly moving and analyzing the CNS for damaged neurons, plaques, and infectious agents; whenever an anomaly is detected, microglia enter an active state and undergo several morphological changes including the thickening and retraction of branches, the expression of immunomolecules, the secretion of cytotoxic factors, recruitment molecules and pro-inflammatory signaling molecules.
Microglial activation is therefore present early in any pathological state of the brain and the in-vivo detection of microglial activation is a key diagnostic aim. Besides, microglia chronic activation has also been suggested as a key factor in the inception and/or progression of neurodegenerative diseases like Alzheimer?s disease and Parkinson?s disease. This project aims at delivering an optimal imaging biomarker for microglia using Positron Emission Tomography (PET) technology. PET is a Nuclear Medicine modality that is able to image the distribution of radioactive labelled compounds. The interest in imaging microglia with PET radiotracers is such that more than 50 radiotracers targeting microglia are now proposed world-wide. In the context of this training proposal, we will test the most promising PET microglia tracers, devise appropriate data-processing procedures and metrics that will allow the selection of the optimal marker to be used in the future in diagnostics, research and drug development.
Technical Summary
The main aim of this research proposal is to shape a Post-Graduate Training Program in PET Methodology focused on the mathematical modelling of novel TSPO tracers in the normal and diseased brain. The TSPO is consistently expressed in the active microglia population in response to mild, acute or chronic brain injury. Microglia are the resident immuno-competent cell of the central nervous system and, in their active state, release pro-inflammatory molecules that initiate and sustain the immune response. This state is generally referred to as ?Neuroinflammation?. Microglia activity is not only regarded as the most sensitive marker of brain disease but it has also been proposed as pathogenic agent in neurodegenerative diseases, Alzheimer?s and Parkinson?s disease in particular. In-vivo TSPO imaging using PET started more than 20 years ago using 11C-PK11195, a positron emitter labelled antagonist for the TSPO but, because of the poor sensitivity of this tracer, research for novel TSPO tracers has surged in the last 5 years with more than 50 new PET TSPO-markers under various stages of clinical validation. It is because of this exceptionally large number of novel tracers and the importance of neuroinflammation for the clinical neurosciences that we define as the main objective of the proposed training program the identification of the optimal TSPO PET probe(s) and of the associated quantitative methodology.
The training program is proposed in three phases. The first one (3 months) will provide the trainee with the basic knowledge on PET methodology. The second phase, (21 months) will consist in a set of 3 months supervised research projects, that will look at various aspects(biological/pathology/chemical/kinetic) of novel TSPO ligands and supply data to a metric (the elaboration of which is one of the research questions) that will inform on the best amongst all candidates and on its quantification procedure. The last phase of the research program (24 months) will be carried out independently by the trainee in the field of TSPO data quantification and will make use of the wealth of clinical and pre-clinical data available at the participating PET centres. We believe that this proposal has unique strengths in the form and content of the training program, in the relevance of the theme for the neurosciences, in the quality and breadth of experience in PET Methodology of the proponents, and the strong academic/industrial partnership (Imperial/GSK) that characterizes the environment.
The training program is proposed in three phases. The first one (3 months) will provide the trainee with the basic knowledge on PET methodology. The second phase, (21 months) will consist in a set of 3 months supervised research projects, that will look at various aspects(biological/pathology/chemical/kinetic) of novel TSPO ligands and supply data to a metric (the elaboration of which is one of the research questions) that will inform on the best amongst all candidates and on its quantification procedure. The last phase of the research program (24 months) will be carried out independently by the trainee in the field of TSPO data quantification and will make use of the wealth of clinical and pre-clinical data available at the participating PET centres. We believe that this proposal has unique strengths in the form and content of the training program, in the relevance of the theme for the neurosciences, in the quality and breadth of experience in PET Methodology of the proponents, and the strong academic/industrial partnership (Imperial/GSK) that characterizes the environment.
Organisations
- King's College London, United Kingdom (Lead Research Organisation)
- University of Oxford, United Kingdom (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- Aarhus University Hospital (Collaboration)
- University of Glasgow, United Kingdom (Collaboration)
- Imperial College Healthcare NHS Trust (Collaboration)
- University of Cambridge (Collaboration)
- Cardiff University, United Kingdom (Collaboration)
- Johnson & Johnson Ltd, United Kingdom (Collaboration)
- University of Sussex, United Kingdom (Collaboration)
- Massachusetts General Hospital (Collaboration)
- Imanova (Collaboration)
- H. Lundbeck A/S (Collaboration)
- Royal Veterinary College, United Kingdom (Collaboration)
- Houston Methodist Research Institute (Collaboration)
People |
ORCID iD |
Federico Edoardo Turkheimer (Principal Investigator) |
Publications

Albrecht DS
(2018)
Pseudoreference Regions for Glial Imaging with 11C-PBR28: Investigation in 2 Clinical Cohorts.
in Journal of nuclear medicine : official publication, Society of Nuclear Medicine

Bhattacharyya S
(2017)
Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.
in Scientific reports

Bloomfield PS
(2016)
Response to Narendran and Frankle: The Interpretation of PET Microglial Imaging in Schizophrenia.
in The American journal of psychiatry

Castellaro M
(2017)
A Variational Bayesian inference method for parametric imaging of PET data.
in NeuroImage

Cuhlmann S
(2014)
In vivo mapping of vascular inflammation using the translocator protein tracer 18F-FEDAA1106.
in Molecular imaging

Di Biase MA
(2017)
PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.
in Translational psychiatry

Edison P
(2013)
Microglia, amyloid, and glucose metabolism in Parkinson's disease with and without dementia.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Fan Z
(2018)
Parametric mapping using spectral analysis for 11C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects.
in European journal of nuclear medicine and molecular imaging

García-Lorenzo D
(2018)
Validation of an automatic reference region extraction for the quantification of [18F]DPA-714 in dynamic brain PET studies.
in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Gatliff J
(2017)
A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling.
in Cell death & disease
Title | Neuroscience and Graphic Design |
Description | This is a digital image library to improve peer-to-peer scientific graphical communication |
Type Of Art | Artefact (including digital) |
Year Produced | 2017 |
Impact | Linked to this initiative we organised a set of workshop to improve the creation of scientific and conceptual figures. A description of the event is reported here: https://neuroscience-graphicdesign.com/workshops/ |
URL | https://neuroscience-graphicdesign.com |
Description | Glaxo Smithkline - Excellence in Imaging Centre |
Amount | £400,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 06/2017 |
End | 08/2019 |
Description | Innovative Medicine Initiative (IMI) |
Amount | € 8,838,000 (EUR) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 11/2016 |
End | 10/2021 |
Description | New Investigator Research Grant |
Amount | £459,272 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2016 |
End | 05/2019 |
Description | Strategic Award: Neuroinflammation in Alzheimer's Disease and Depression |
Amount | £1,720,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2019 |
Description | Targeting neuroinflammation in schizophrenia |
Amount | £841,703 (GBP) |
Funding ID | MR/N027078/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Dementia (NIMA). |
Amount | £5,000,000 (GBP) |
Funding ID | 104025/Z/14/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2017 |
End | 12/2018 |
Title | Biomathematical modelling approach |
Description | This modelling approach is developed to predict the in vivo performance of radioligands from in vitro/in silico data. |
Type Of Material | Model of mechanisms or symptoms - human |
Provided To Others? | No |
Impact | This model assisted experimental design for TSPO imaging by estimating the in vivo reproducibility of the radioligand and the sample sizes/power required by the experiment. |
Title | PK modelling |
Description | Different pharmacokinetic models have been applied in the analysis of in vivo PET data. |
Type Of Material | Model of mechanisms or symptoms - human |
Provided To Others? | No |
Impact | Different models were used to quantify to TSPO binding in human brain in healthy volunteers and MS patients, and specifically the double input models identified the metabolite issues with tracers. |
Title | Statistical tool for PET experimental design |
Description | A statistical modelling approach to estimate sample size required for longitudinal and disease characterisation studies using PET. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2011 |
Provided To Others? | Yes |
Impact | The methods have been used to assist in the experimental design of more than 8 in vivo PET studies on neuroinflammation. |
Title | in vivo PET scans wit 18F-PBR111 |
Description | These PET scans were funded by GSK and performed by GSK and Imanova, which allows for the evaluation of different quantification methodology of TSPO imaging. |
Type Of Material | Biological samples |
Provided To Others? | No |
Impact | These vivo imaging data is the first time in human data that TSPO/neuroinflammation that has been detected using 18F-PBR111. This tracer produced higher total signal than the traditional tracer 11C-PK11195. The in vivo uptake is consistent with genetics. |
Title | in vivo PET study with 11C-PBR28 |
Description | in vivo PET scans using 11C-PBR28 with arterial blood samples |
Type Of Material | Biological samples |
Provided To Others? | No |
Impact | The in vivo TSPO uptake is consistent with genetics |
Description | Aarhus Hospital |
Organisation | Aarhus University Hospital |
Country | Denmark |
Sector | Hospitals |
PI Contribution | We analysed the PET data using the SUPERPK approach developed by our team. |
Collaborator Contribution | Aarhus Hospital provided us clinical PET data of patients who has spinal cord injury; |
Impact | In vivo PET data has been analysed to investigate the inflammation associated with spinal cord injury. This is a multi-disciplinary collaboration as it covers area of medicine, neurology, imaging and quanfication. |
Start Year | 2010 |
Description | Dr. Paolo Zanotti-Fregonara (University of Bordeaux, Fr) |
Organisation | Houston Methodist Research Institute |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | Dr. Zanotti-Fregonara shared with us his PET datasets (acquired in collaboration with National Institutel of Mental Health). With this data we had the opportunity to test and validate some of the new modelling approaches for quantification of neuroinflammation PET tracers that are currently in use for tracers like 11C-PBR28. |
Collaborator Contribution | The role of Dr. Zanotti-Fregonara in this collaboration has not been limited to sharing the data. He actively interacts with us to elaborate new theories about the role of neuroinflammation in many diseases and disorders of the central nervous system. These reasearches are still ongoing |
Impact | Peer reviewed publications and conference proceedings |
Start Year | 2013 |
Description | Elucidation of the Neuronal Cell Biology of the Neuroimaging Tool TSPO |
Organisation | Royal Veterinary College (RVC) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We stimulated the connection to include neurodegenerative phenotype in the analysis which is being progressed. |
Collaborator Contribution | The team lead by Dr. Michelangelo Campanella has obtained the following informations: The 18-kDa protein TSPO localizes on the outer mitochondrial membrane (OMM). Over-expressed at sites of neuroinflammation it is adopted as a biomarker of cell and tissue pathology in the brain. TSPO undermines the autophagy-mediated removal of mitochondria by limiting the PARK2 ubiquitination via accumulation of the Reactive Oxygen Species (ROS). In this work we describe the source of ROS to be secondary to a Ca2+ signaling deregulation. In TSPO overexpressing cells VDAC1 is thus phosphorylated by the Protein Kinase A (PKA), which is recruited to mitochondria, in complex with the Golgi-derived protein, Acyl-CoA binding domain containing 3 (ACBD3). The inhibited mitochondrial Ca2+ uptake leads to a parallel increment in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) increasing ROS: a molecular cascade reassembled by in vitro models of glutamate excitotoxicity. A novel OMM based pathway to control intracellular Ca2+ and redox signaling is here outlined and a mechanism of mitochondrial adaptation to cytotoxicity proposed. |
Impact | This work has generated three presentations at International Conferences listed as follow: 1- 59th Biopshyical Society Meeting 2015, Baltimore USA 2-2nd Cell Focused Meeting on Mitochondria 2015, Chicago USA 3-60Th Biophysical Society Meeting 2015, LA, USA One original research manuscript currently under revision in the Journal of Molecular Cell Biology |
Start Year | 2014 |
Description | GlaxoSmithKline and Imanova |
Organisation | GlaxoSmithKline (GSK) |
Department | GSK Clinical Imaging Centre (CIC) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We used the PET data from this GSK study produced by Imanova to develop methodology for the quantification of neuroinflammation in both healthy subjects as well as MS, and HIV patients and alcohol independent subjects. |
Collaborator Contribution | GSK provided us both in vitro and in vivo clinical PET data, which allows for the development of methodology for neuroinflammation imaging. Imanova provided imaging facilities and human resources to perform the GSK MS study with the 2nd generation radioligands. |
Impact | A biomathematical modelling approach has been developed to predict ligand performance based on in vitra data. In vivo PET data of both healthy subjects and patients have been analysed and different methodology are being evaluated. This is collaboration is multi-disciplinary and requires the contribution from all the expertise from methodology development, quantification, neurology, chemistry, biology and physics. |
Start Year | 2010 |
Description | Inflammation in pituitary tumour |
Organisation | Imanova |
Country | United Kingdom |
Sector | Private |
PI Contribution | PET methodology development for investigating TSPO expression in pituitary gland for oncology |
Collaborator Contribution | In vitro/ ex vivo experiments and in vivo PET scans |
Impact | In vivo TSPO expression has been evaluated in a small sample of subjects using 2nd generation TSPO PET tracer 11C-PBR28. |
Start Year | 2012 |
Description | Inflammation in pituitary tumour |
Organisation | Imperial College Healthcare NHS Trust |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | PET methodology development for investigating TSPO expression in pituitary gland for oncology |
Collaborator Contribution | In vitro/ ex vivo experiments and in vivo PET scans |
Impact | In vivo TSPO expression has been evaluated in a small sample of subjects using 2nd generation TSPO PET tracer 11C-PBR28. |
Start Year | 2012 |
Description | NIMA Consortium Project |
Organisation | Cardiff University |
Department | Psychiatry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | H. Lundbeck A/S |
Country | Denmark |
Sector | Private |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | Johnson & Johnson |
Department | Janssen Pharmaceuticals |
Country | United States |
Sector | Private |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | University of Cambridge |
Department | Wolfson Brain Imaging Centre |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | University of Glasgow |
Department | Mental Health and Wellbeing Glasgow |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | University of Oxford |
Department | Department of Psychiatry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | NIMA Consortium Project |
Organisation | University of Sussex |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint partners in the Wellcome NIMA consortium |
Collaborator Contribution | Joint partners in the Wellcome NIMA consortium |
Impact | The project, which has received a Strategic Award of £5 million (to be awarded in milestones) from the Wellcome Trust, is a new public-private partnership between seven universities (Cambridge, Cardiff, Glasgow, King's College London, Oxford, Southampton and Sussex) and the companies Janssen Research Development LLC and H. Lundbeck A/S (Lundbeck). The project has been facilitated by Johnson & Johnson Innovation in London. The initial link between the immune system and psychiatric and neurodegenerative disorders has been established by a number of studies which indicate that increased levels of biological markers for inflammatory processes are found in patients with depression and Alzheimer's disease. It has also been shown that inflammatory processes can trigger phenomena that resemble mood disorders or neurodegeneration in some cases. However, whether or not anti-inflammatory medicines could benefit patients remains unclear. In a two-stage project, the team will begin by investigating the immune system of patients with depression that has not responded to conventional treatment and patients with Alzheimer's disease. They also plan to use animal models to establish more precisely what the relationship is between immune-related markers found in blood and brain function and behaviour. The second part of the research, which is reliant on the success of the first, will be to carry out "proof-of-concept" experimental medicine trials, using re-purposed anti-inflammatory drugs in patients who have been identified according to their specific immunological profile. |
Start Year | 2014 |
Description | Neuroinflammation and Pain |
Organisation | Massachusetts General Hospital |
Department | Martinos Center for Biomedical Imaging Massachusetts |
Country | United States |
Sector | Hospitals |
PI Contribution | We provided methodological support for the quantification of PET TSPO data in chronic pain studies. |
Collaborator Contribution | Prof Marco Loggia has provided us with both PET and fMRI data on a variety of chronic pain conditions where we are testing our virtual histology methodology |
Impact | The project is still ongoing. So far the following has been published: Albrecht DS, Normandin MD, Shcherbinin S, Wooten DW, Schwarz AJ, Zürcher NR, Barth VN, Guehl NJ, Akeju O, Atassi N, Veronese M, Turkheimer F, Hooker JM, Loggia ML. Pseudoreference Regions for Glial Imaging with 11C-PBR28: Investigation in 2 Clinical Cohorts. J Nucl Med. 2018 Jan;59(1):107-114. |
Start Year | 2018 |
Company Name | Imanova Ltd |
Description | Imanova is an innovative alliance between the UK's Medical Research Council and three world-class London Universities: Imperial College, Kings College and University College. Established in April 2011 as an independent company, Imanova and its partners bring together a breadth and depth of knowledge and expertise that will drive research and innovation in imaging sciences. Imanova will have a real impact on human health and the understanding of disease. Imanova now owns and manages the renowned Clinical Imaging Centre (CIC) located at Imperial College London's Hammersmith Hospital campus. This state of the art facility was developed by former owner GlaxoSmithKline, and has benefitted from £47million of investment in equipment and infrastructure since opening in 2007. |
Year Established | 2011 |
Impact | Close collaboration on developing molecular imaging probes for neuroinflammation |
Website | http://www.imanova.co.uk/ |
Description | Imaging MS Workshop |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | 40 Attendees. Sparked joint research activities and joint grant applications. Wider awareness of molecular imaging technology available for imaging Multiple Sclerosis in the UK |
Year(s) Of Engagement Activity | 2013 |
Description | KCL Molecular Neuroimaging YouTube Channel |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | We have created a YouTube channel where we have installed a series of introductory lectures as well as short pieces presenting to the interested public our research work |
Year(s) Of Engagement Activity | 2017,2018 |
URL | https://www.youtube.com/channel/UCCu_TK13NmIU8LXIFj_XU7A |
Description | PET Pharmacolkinetic Course 2013 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | 50 students from academic institutions and pharmaceutical companies with different background(chemistry, biology, pharmacology, physics) attended the course, studied pharmacokinetics for PET imaging and performed computer exercises. Students provide very good feedback of the lectures, exercises and discussion. The course benefits the students' understanding of the quantification of PET studies. |
Year(s) Of Engagement Activity | 2007,2008,2009,2010,2011,2012,2013 |
URL | http://www2.kenes.com/brain2013/scientific/Pages/PET_Pharmacokinetics_Course.aspx |