PET neuroimaging, a cross-cutting theme
The MRC NMHB has been leading an initiative to facilitate UK positronic emission tomography (PET) imaging research in the CNS neurosciences. Radioligand PET is an essential tool in translational medicine and for aspects of new drug development, particularly drugs for neurological and psychiatric indications.
Along the translational medicine developmental pathway, PET radiotracers are used for diagnosis, as a tool for drug development and to gain a better understanding of disease biology. The main uses are:
- Dose-finding for new agents
- Definition of populations in terms of brain abnormalities, especially receptors and enzymes
- As a surrogate marker for treatment effects
- Proof of concept studies in normal volunteers or patient populations
The first ever community workshop of neuroscientists using PET imaging was held by the board in May 2008. The participants had never previously met as a group. Some findings of the workshop were specific to neurosciences while other findings have broader relevance for PET research in other scientific areas: primarily cancer but also cardiovascular disease. Download the workshop report.
Broadly speaking, UK strengths include:
- World class PET expertise
- Skill/knowledge base in the UK for world-class translational research in neurosciences
- Strong NHS/academic partnerships and possibilities for collaboration with pharma
- Emerging multi-centre networks for all aspects of PET
The perceived challenges for the UK are:
- Methodology needed for efficient screening of candidate compounds and better access to libraries
- Training, recruitment and retention of radiochemists, chemists, modellers, cyclotron engineers and people with Good Manufacturing Process (GMP) / Quality Assurance (QA) expertise
- Navigating regulatory issues
- Lack of GMP facilities and need for routine availability of ligands for multicentre trials.
For PET neuroscience imaging, an important distinguishing feature is that the image is less important than the ability to obtain quantitative pharmacokinetic and pharmacodynamic data. In oncology, PET primarily supplies the image of the tumour required for diagnosis and radiochemistry.
NMHB strategy development is ongoing and has focused on three areas – building capacity, regulatory issues and finding the best routes for working with industry:
Building capacity: A call for proposals led to three awards in July 2009 made under a new MRC specialist postdoctoral training pilot programme in PET neuroscience. Two awards are held at Imperial College London, one at the University of Cambridge. Successful awardees have been asked to establish a NeuroPET network so that UK resources can be pooled for the common good. More details are available on page 12 of MRC Network Jan-Feb 2010. A further call was launched in 2012 and the successful awards will be announced in March 2013.
Regulatory issues: The MRC is working with partners from the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Cancer Research Institute towards building a regulatory relationship and enabling environment for PET based research in UK. As a result of these discussions, a workshop for PET imaging researchers was held in September 2010 at MRC. UK PET researchers from the neurosciences, cardiovascular sciences and cancer fields were involved; a note of this workshop is available here. Papers produced for this meeting included a decision tree as to whether a clinical trial authorisation is required and some examples of study scenarios. These documents are also available on the NCRI-PET Research Network website which also includes some frequently asked questions. The MHRA is taking forward this work through a programme of further interactions with the community and they also have PET specific pages on their website:
More information on the MHRA PET Panel.
Industry issues: To advance translational research, researchers must seek ways to strengthen industry-academic collaboration in the context of international competition. After a consultative meeting with industry scientists in June 2009 possible models for academic-industry centres for PET imaging were under discussion. Imanova was announced in April 2011 and is a unique partnership between the MRC, Imperial College London, King’s College London and UCL. The partners are equal shareholders in a venture that assumed responsibility for the facilities and operations of GSK’s £47m Clinical Imaging Centre at the Hammersmith Hospital campus. Further information on Imanova is available on their website.
In essence, the MRC is seeking to facilitate better interaction between industry and academia, enhance communication between researchers and regulators, and find ways to cut any unnecessary red tape. The goal is to make UK PET imaging research more internationally competitive.