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Imaging Chemistry and Biology (pre-2019)

New routes to carbon-11 based molecular imaging agents for in vivo PET imaging

Project ID: 2015_206

Student: Joseph Downey

1st supervisor: Tony Gee, King’s College London
2nd supervisor: Ran Yan, King’s College London

Positron emission tomography (PET) imaging is a powerful tool for disease diagnosis, understanding in-vivo biomechanisms, and in drug discovery and development. PET Imaging probes are labelled with cyclotron-produced short-lived positron-emitting radionuclides (eg. carbon-11 and fluorine-18, radioactive half-lives 20 min and 110 min, respectively) using rapid labelling techniques. A major confounding factor in developing new radiolabelled PET probes is the limited number of labelled starting materials available from the cyclotron. Recently the use of labelled carbon monoxide has generated much interest in the synthesis of PET imaging probes because the versatility of the metal-mediated carbonylation chemistry allows access to a plethora of labelled carbonyl compounds of biological interest. However, the availability of labelled carbon monoxide as a synthetic starting material at PET sites internationally is limited to a few research sites because of the need for specialist infrastructure for its conversion from cyclotron-produced carbon monoxide, precluding the wider utilisation of this attractive labelling approach.

This proposal aims to overcome this obstacle by harnessing the properties of Chlorosilanes (Friis et al – J. Am. Chem. Soc. 2011, 133, 18114–18117) as carbon dioxide trapping and reducing agents, obviating the need for specialist infrastructure to perform carbon monoxide radiolabelling procedures (a small scale pilot study in our lab indicate that this may be a viable approach and warrents further investigation). The project will aim to synthesis a library of chorosilanes which will be examined for their propensity to trap and reduce 11C-carbon monoxide and release 11C-CO in a rapid and convenient manner. The technique will then be tested in the radiosynthesis of carbonyl-containing compounds of biological interest and will involve a medicinal chemistry component to the project. The imaging properties of the radiolabelled candidates will be initially evaluated in vitro. Promising 11C-labelled compounds may be evaluated in vivo during the course of the project.

The project will be run in close collaboration with PMB, a subsidiary of the group ALCEN engaged  in various sectors, such as the healthcare, the aerospace, the defence the electronics, the nuclear power and the scientific research. PMB is specialized in the design and manufacturing of particles accelerators for medical applications, with a specific focus on the cyclotron and associated technologies used for the Positron Emission Tomography. PMB is engaged in the development of an innovative PET Imaging Biomarkers production solution, based on a new fully micro & milli-fluidic synthesize system, to be proposed to researchers and clinicians.

Based on King’s expertise in radiochemistry and its ability of developing tracers for PET, PMB & King’s have decided to join efforts to co-develop the innovative solution, on the technology, on the radiochemistry and on the integration of new tracers into microfluidic systems. PMB & KCL believe that the field of PET needs a new generation of scientists and clinicians with a deeper and wider understanding of the real value of PET.

This PhD program will provide the student the expertise and skills sought after by this scientific community. The training will provide the student with unique skills in radiochemistry, microfluidics, radiochemistry instrumentation, radioanalytical techniques, purification science, synthetic medicinal chemistry, in vitro and in vivo radiobiology (eg autoradiograophy, microPET scanning) and pharmacology in addition to unique industrial and international networking opportunities.

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