1st Supervisor: Prof Tony Gee, King’s College London
2nd Supervisor: Dr Philip Miller, Imperial College London
Clinical supervisor: Dr Paul Edison, Imperial College London
Aim of the PhD Project:
- To enable the 11C-labelling of amino acids with high stereoselectivity, radiochemical yield and in short reaction times.
- To develop shelf-stable amino acid-palladium complex precursors that will react with 11CH3I and 11CO in order to rapidly generate 11C-amino acids.
- To measure the efficiency and expand the capability of this labelling process to a range of natural and unnatural amino acids, and peptides.
Lay summary:
Natural amino acids are the building blocks of peptides and proteins, however, they also have implications for signaling between cell types in our bodies. The development of amino acid imaging probes has been a major area for imaging sciences over the past decades and still presents challenges and opportunities. This project aims to develop new labelling methods that will enable access to a range of natural and unnatural 11C-amino acids using the common 11C-labelling precursors 11CH3I and 11CO. Labelled amino acids have been most widely used as ligands for a imaging a range of cancers (e.g. [11C]methionine for glioblastoma) and neurological conditions (e.g. [18F]DOPA for Parkinson’s). Despite their simple chemical structures, amino acids can be highly challenging to radiolabel. This is in part due to the low reactivities of labelling precursors, the need for stereoselectivity and issues with purification. One of our key aims will be develop Pd-amino acid precursors of amino acids that will enable C-H activation and resultantly fast reactions with carbon-11 precursors.
The candidate for this project should have a synthetic chemistry background.
References
- A. Pekošak, U. Filp, A. J. Poot, A. D. Windhorst, Mol. Imaging Biol. (2018) 20:510–532
- A. Sun, X. Liu and G. Tang; (2018) Front. Chem. 5:124.