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EPSRC Reference: EP/E039278/1
Title: Microfluidic Devices Applied to the Synthesis of [11C]methyl Labelled Molecules of Biological Interest for Positron Emission Tomography (PET)
Principal Investigator: Miller, Dr P
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: Imperial College London
Scheme: Postdoc Research Fellowship
Starts: 01 August 2007 Ends: 30 November 2010 Value (£): 277,292
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Biomedical neuroscience
Catalysis & Applied Catalysis Microsystems
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
09 Feb 2007 LSI Postdoctoral Fellowships Sift Panel 2007 InvitedForInterview
Summary on Grant Application Form
Positron Emission Tomography (PET) is a field of medical imaging that uses radioactive compounds to make images and obtain information about diseases, such as cancer, in the human body. PET is used to trace where special types of radioactively labelled compounds distribute, accumulate and breakdown in the body. This information is extremely useful when developing new drugs for disease treatment and diagnosis because it can allow the identification of possible drug candidates at an earlier stage of the drug development process. During a PET scan a radioactive compound is injected into a live subject (animal or human), the radioactive compound rapidly decays and gives out radiation of a know energy which travels out through the body. This radiation, in the form of photons, is detected by the PET scanner and transformed into images that give us information about the distribution and concentration of the radiotracer in the subject's body. The synthesis of radiolabelled compounds for use in PET scans is particularly challenging due to the short half-lives of the common radionuclides used in PET, for example [11C]carbon has a half-life of only 20.4 min. Normally radiosyntheses for PET have to be carried out within three half-lives to provide enough radioactivity to do a scan, (within 60 mins for 11C). New methods and strategies for rapidly conducting radiochemical reactions and improving radiolabelling for new PET tracers are essential for future drug development and disease treatment. This research proposal aims to synthesise new tracers, for use in PET scans, rapidly and efficiently using a microfluidic reaction system and newly developed catalysts to enhance the rates and radiochemical yields of important reactions used in 11C labelling. Catalysts can have a remarkable influence over yields, rates and selectivities of chemical reactions. It is therefore vitally important to choose the most effective catalyst for a specific chemical reaction, this is even more apparent when the reactions under study have to be completed in extremely short reactions as in the synthesis of radiolabelled compounds. New and existing catalysts, based on a highly active palladium(I) complex, will be screened for the methylation reaction with particular emphasis on identifying catalysts that give high yields during the early stages of reactions. Once the best catalysts have been identified they will used in radiolabelling experiments using a microreactor system. Miniaturised reactor systems or microreactors are ideally suited for radiosyntheses due to the extremely small amounts reagents used in these reactions; typically sub-micromolar quantities of radioactive compounds are produced. In addition, the added benefits of enhanced heat and mass transport observed within such micro-systems may result in better yields in shorter reaction times. This system will be applied to the reaction of [11C]methyl iodide (a commonly used reagent in PET) with certain precursors that will be used to form a series of drug candidates which have the potential to bind to specific receptors in the central nervous system. The class of candidate molecules to be synthesised is particularly interesting since they have recently been developed as selective, high-affinity ligands for receptors that have been associated with a number of central nervous system disorders, including schizophrenia, anxiety, depression, Parkinson's disease, addiction and pain. Improved strategies to radiolabelling new candidate molecules that target these receptors and their study using PET scans will lead to a greater understanding of drug-receptor binding and may lead to the development of new drugs to treat central nervous system disorders.
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