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Imaging Chemistry and Biology (pre-2019)

Imaging and sensing in living cells using dual modality fluorescent PET imaging agents

Project ID: 2017_202

Student: Rian Hendley

1st supervisor: James Wilton-Ely, Imperial College London
2nd supervisor: Tony Gee, King’s College London

Positron Emission Tomography (PET) is a powerful technique, used particularly in oncology, which allows three-dimensional imaging of tissue deep in the body (2 million scans in the US each year). However, substantial infrastructure is required for (often short-lived) radioisotope generation. Incorporating fluorescence within the same agent allows imaging through the emission of visible light to indicate the location of the agent. Adding targeting units to the probe ensures high selectivity for tumours, thus creating a targeted, dual modality agent for the imaging of cancer. Importantly, this will allow visualisation of the tumour site before an invasive procedure (using PET) and, once radiation is no longer present, during surgery (using the fluorescence). The inbuilt flexibility of the system proposed will allow many different types of tumours to be targeted selectively using different targeting groups attached to the metal centre. This will enhance the potential for clinical translation and future commercial development.

It has only recently been established that our bodies naturally produce and use carbon monoxide as a gaseous messenger. Using their fluorescence response, the same probes will also be investigated for the real-time monitoring of carbon monoxide in this role. Based on related systems we have developed (J. Am. Chem. Soc. 2014, 136, 11930), such systems could solve the problems of low sensitivity and response speed which undermine current approaches in this new field. In addition, the presence of abnormal levels of endogenous carbon monoxide has been shown to be a marker of disease.

This multidisciplinary project provides scope for the PhD student to develop skills in coordination chemistry, ligand synthesis, radiochemistry (11CO), PET imaging and cell culture. It is not expected that the student will have prior experience in all these areas but some background in synthesis will be an advantage. Training in all relevant aspects will be provided in the two groups at Imperial College and St. Thomas’ hospital.

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