MRC Collaborative Training Programme in Radiochemistry for NeuroPET

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

Positron emission tomography or PET allows the amount and position of specific molecules to be mapped non-invasively using sensitive detectors of very low level, relatively safe radioactively tagged tracers. In the ideal case, the method could provide critical diagnostic information for the diagnosis of major diseases such as Alzheimer s disease long before symptoms may appear. The methods also can be used to help better ensure that the right dose of experimental drugs are used in clinical trials, increasing the likelihood of successful completion of the trials. However, while the UK has equipment that could allow a high level of this activity at several major academic hospitals, there are not enough chemists specially trained to develop and produce the radiotracers. This proposal would create a novel 4 year training programme- really a world first - to equip two chemists with the skills and experience to become UK leaders in this area. In addition, the grant will bring together centres that previously have not worked together, allowing them to begin to pool resources for common good.

Technical Summary

This proposal is to establish a pilot advanced neuroPET radiochemistry training programme linking major centres for molecular imaging in the UK in a collaborative network. The programme will be aimed at post-doctoral chemists. Two four-year training fellowships will be created by our programme. The initial two years of each will be focused on developing foundation skills in a structured, ?hands-on? pedagogical framework. In the latter six months of this two-year foundation training period, trainees will take on a mentored evaluation of potential approaches for new neuroPET radiotracer refinement or development. In the final two years of the programme, trainees then will work in one of the collaborative sites as the lead in a programme to develop one such radiotracer concept. The new radiotracer development will be pursued in a way that will allow the rapid translation of the work to benefit multiple partners in the collaborative network (and others). The outcomes of this programme will include new collaborative partnerships between UK molecular imaging centres, newly trained radiochemists able to lead independent programmes and a contribution to the development or refinement of novel PET molecular imaging radiotracers.

Publications

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Colasanti A (2014) In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET. in Journal of nuclear medicine : official publication, Society of Nuclear Medicine

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Datta G (2017) C-PBR28 and F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis. in Journal of nuclear medicine : official publication, Society of Nuclear Medicine

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Guo Q (2013) Quantification of the specific translocator protein signal of 18F-PBR111 in healthy humans: a genetic polymorphism effect on in vivo binding. in Journal of nuclear medicine : official publication, Society of Nuclear Medicine

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Matthews PM (2013) Technologies: preclinical imaging for drug development. in Drug discovery today. Technologies

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Matthews PM (2014) The emerging agenda of stratified medicine in neurology. in Nature reviews. Neurology

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Matthews PM (2012) Positron emission tomography molecular imaging for drug development. in British journal of clinical pharmacology

 
Description Engagement with MHRA for establishing an expert or "superuser" group to help the UK community best respond to MHRA guidelines for PET
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Post-Weatherall Panel to review UK Primate Research
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Refinement of review procedures
 
Description Public consultation roll out of participant involvement in research- MRC/WT sponsorted
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Changes in perception of clinical trials
 
Description WT-GSK Clinical Training Fellowships
Amount £2,750,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2008 
End 08/2017
 
Title Evaluation of IL2 as a fluorinated PET tracer 
Description IL2 can be a used as a molecular probe for T-cells in humans. The work refined and evaluated a method for preparation that had been described by European collaborators. Unfortunately, we proved it to degrade the molecule and hence are developing new approaches. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact The work has informed R and D in GSK, which had been intending to apply the F-IL2 tracer 
 
Title Implementation of radiotracers for research use 
Description A number of radiotracers were newly implemented in the UK Imanova centre including rolipram, PBR28, PBR111 and additional work was done to make PE2I avaliable. 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact GSK and Imperial college based resarchers are starting or preparing to start clinical studies. 
 
Description Birmingham 
Organisation University of Birmingham
Department College of Life and Environmental Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided scanning facility, expertise in design, execution, analysis and interpretation
Collaborator Contribution Staff and collaborative approach to problem
Impact Univ Birmingham successfully submitted bid for their own imaging centre, which is thriving
 
Description GlaxoSmithKline Global Imaging Unit 
Organisation GlaxoSmithKline (GSK)
Department GSK Clinical Imaging Centre (CIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Wellcome Trust-GSK Clinical Fellowships in Translational Medicine
Collaborator Contribution Financial support and co-mentorship for students
Impact 16 clinical fellows have been enrolled or have completed Academic papers and 1 patent have resulted
Start Year 2007
 
Description Psychiatry 
Organisation University of Oxford
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution Helping to define problem, experimental design, analysis, implrementation and interpretation
Collaborator Contribution Staff
Impact Multiple papers- support for new grants to Profs. Cowen and James
Start Year 2006
 
Description Training collaboration 
Organisation GE Healthcare Limited
Department Nuclear Medicine
Country United Kingdom 
Sector Private 
PI Contribution The research team joined with those from GE Amersham, The Wolfson laboratory at Manchester and Newcastle University to share information on PET radioligand approaches. Direct interactions now have been scheduled to continue.
Collaborator Contribution Advice Joint planning for new radiotracer implementationProvided a training and collaborative environment
Impact None
Start Year 2010
 
Description Training collaboration 
Organisation Imanova
Country United Kingdom 
Sector Private 
PI Contribution The research team joined with those from GE Amersham, The Wolfson laboratory at Manchester and Newcastle University to share information on PET radioligand approaches. Direct interactions now have been scheduled to continue.
Collaborator Contribution Advice Joint planning for new radiotracer implementationProvided a training and collaborative environment
Impact None
Start Year 2010
 
Description Training collaboration 
Organisation Newcastle University
Department Radiochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution The research team joined with those from GE Amersham, The Wolfson laboratory at Manchester and Newcastle University to share information on PET radioligand approaches. Direct interactions now have been scheduled to continue.
Collaborator Contribution Advice Joint planning for new radiotracer implementationProvided a training and collaborative environment
Impact None
Start Year 2010
 
Description Training collaboration 
Organisation University of Manchester
Department Wolfson Molecular Imaging Centre (WMIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution The research team joined with those from GE Amersham, The Wolfson laboratory at Manchester and Newcastle University to share information on PET radioligand approaches. Direct interactions now have been scheduled to continue.
Collaborator Contribution Advice Joint planning for new radiotracer implementationProvided a training and collaborative environment
Impact None
Start Year 2010
 
Title GlaxoSmithKline Early Development 
Description Over last 5 years, research and group have contributed to development of more than 18 different molecules in early development (see letter from Dr. Phil Murphy in 2013 REF submission). Here these contributions all have been "lumped" into a single entry 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Actively seeking support
Impact reducing costs for commercial development, increased competitiveness of UK environment 
 
Company Name Imanova, Ltd. 
Description Imanova is a molecular and functional imaging service company. This funding programme further demonstrated the value of public-private partnerships in this area to GSK, who led in formation of the new company. The programme continues to support Imanova and is not providing the latter with a model for training. 
Year Established 2011 
Impact Has established proof of principle for training in radiochemistry in the context of this kind of company
Website http://www.imanova.co.uk/
 
Description Cold Spring Harbour Interdisciplinary Art and Science meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Supporters
Results and Impact Educated artists,writers in methods of science

Follow up invitation to 2013 ICLA
Year(s) Of Engagement Activity 2012
 
Description Exploring Canada-UK-US Synergies for Medical Imaging, London 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Exploring Canada-UK-US Synergies for Medical Imaging, Canadian High Commission, London, 30 June 2011 -Advanced imaging for experimental medicine in oncology: opportunities and challenges


Improved use of molecular imaging by industry
Year(s) Of Engagement Activity 2011
 
Description Keynote Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact To present a talk at the Spanish Academy of medicine to an audience of Spanish medical staff.
Year(s) Of Engagement Activity 2017
 
Description MRC - Japan Science and Technology Collaborative Workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact MRC - Japan Science and Technology Collaborative Workshop, Tokyo, 14 June 2012 - UK Imaging Science: an overview


Commercial engagement with UK academic base
Year(s) Of Engagement Activity 2012
 
Description Showcasing British Neuroscience, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Showcasing British Neuroscience, Wellcome Trust, London, February 2013 - A national effort for translational neuroscience and imaging

Commercial engagement with UK academic base
Year(s) Of Engagement Activity 2013
 
Description UniQ Summer School Lecture and Workshop, Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact UniQ Summer School Lecture and Workshop, University of Oxford - 21 July 2010 - New drugs for the developing world


Expanding access to UK elite universities for school children
Year(s) Of Engagement Activity 2010