About the Project
Over the last years, molecular imaging has become an established technology widely used as a research tool and in healthcare. Due to its unique quantitative features and superior sensitivity in comparison with other imaging modalities, positron emission tomography (PET) has received special attention in the development and validation of biomarkers for brain imaging targets. The industrial partner General Electric (GE) Healthcare has successfully developed a portfolio of 18-F labelled (physical half-life 110 minutes) PET radiotracers for neurologic applications including flutemetamol (for beta amyloid imaging), GE-179 (NMDA ion channels), GE-180 (translocator protein 18kDa), GE-194 (GABA-A) and GE-216 (tau imaging). The academic institution University of Manchester (UoM) has established a Centre for Imaging Sciences specialised in image computing and quantitative analysis of dynamic data. Furthermore animal models have previously been used for the validation and characterisation of novel imaging biomarkers, and PET imaging is currently used in models of stroke, Alzheimer’s Disease and schizophrenia to investigate disease mechanisms.
This collaboration seeks a joint qualification of PET tracers in i) preclinical settings, ii) first in man studies and iii) clinical trials.
i) The preclinical tracer characterisation will be performed in rats at UoM with a particular emphasis on devising quantification methods that overcome the need for blood sampling by making maximum use of image derived input functions and data led techniques to extract reference tissue kinetics in cases where no region devoid of specific binding exists. This would subsequently enable the use of these tracers in quantitative imaging of animal models of disease by facilitating longitudinal studies.
ii) GE sponsors first in man studies of its novel PET tracers in imaging centres worldwide. The data are then analysed at the Grove Centre in Amersham. During the placement of the student at the industrial partner’s site, methods for optimal tracer specific data analysis will be jointly developed and investigated in those pilot data sets.
iii) The High Resolution Research Tomograph (HRRT) at the Wolfson Molecular Imaging Centre (WMIC) of the UoM is the human brain positron camera with the highest spatial resolution in the world providing data with reduced partial volume effect compared to standard clinical cameras. Investigator led studies are conducted to assess the utility of new GE tracers such as GE-180 in direct comparison with predecessors such as [11C](R)-PK11195 for clinical and research applications for example in stroke and multiple system atrophy. This PhD studentship will underpin those clinical trials by developing the best possible imaging and quantification methodology. Clinical research studies are due to commence on the new GE SIGNA PET/MR camera of the UoM paving the way to simultaneous acquisitions combining the strengths of both modalities in brain imaging.
• http://research.bmh.manchester.ac.uk/imagingfacilities
• http://www3.gehealthcare.co.uk/en-GB
This is a potential studentship to be funded via the MRC Doctoral Training Programme. Projects under this scheme are competitively funded; i.e. there are more projects advertised than available.
References
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• Thurfjell, L.; Lilja, J.; Lundqvist, R.; Buckley, C.; Smith, A.; Vandenberghe, R.; Sherwin, P. Automated quantification of 18F-flutemetamol PET activity for categorizing scans as negative or positive for brain amyloid: concordance with visual image reads. J. Nucl. Med. 55 (2014), 1623 - 1628.
• Su, Z.; Herholz, K.; Gerhard, A.; Roncaroli, F.; Du Plessis, D.; Jackson, A.; Turkheimer, F.; Hinz, R. [11C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur. J. Nucl. Med. Mol. Imaging 40 (2013), 1406 - 1419.
• Drake, C.; Boutin, H.; Jones, M.S.; Denes, A.; McColl, B.W.; Selvarajah, J.R.; Hulme, S.; Georgiou, R.F.; Hinz, R.; Gerhard, A.; Vail, A.; Prenant, C.; Julyan, P.; Maroy, R.; Brown, G.; Smigova, A.; Herholz, K.; Kassiou, M.; Crossman, D.; Francis, S.; Proctor, S.D.; Russell, J.C.; Hopkins, S.J.; Tyrrell, P.J.; Rothwell, N.J.; Allan, S.M. Brain inflammation is induced by co-morbidities and risk factors for stroke. Brain Behav. Immun. 25 (2011), 1113 - 1122.