New strategies for the introduction of 18F into peptides for imaging with Positron Emission Tomography

PET is a potent imaging technique that uses positron emitting radionuclides such as 18F, which is used either in the form of [18F]FDG or attached to another biomolecule for diagnosis of disease and monitoring of treatment. The major disadvantage of labelling molecules with 18F is their time-consuming, multiple step preparation. This thesis presents two different novel strategies that both aim to decrease the number of steps required to prepare l8F labelled peptides. The first strategy involved using the metal ruthenium as a binding site for 18F in a one-step labelling technology involving halide anion exchange. The second approach involved a chemoselective reaction between the hydrazine functionalised compounds HYBA or HYNIC and a labelled aromatic aldehyde to form a hydrazone. In the second strategy, a peptide is synthesised with a HYBA or HYNIC molecule attached to it. Following this, F labelled benzaldehyde is reacted with the peptide to give a 1 + 1 labelling strategy. Before using this methodology for labelling with l8F, the chemoselectivity of the hydrazone formation was thoroughly tested by conducting competition reactions. The competition reactions involved a reaction between an aromatic aldehyde and HYBA in the presence of a competing amine. The reaction was found to be selective between the aldehyde and HYBA, even with increased equivalents of the competing amine present in the reaction mixture. Rate monitoring reactions were carried out in the presence of the competing amine, benzylamine, to see how quickly the hydrazone product formed at room temperature and at 50°C. The formation of the hydrazone was found to be quick and clean, even at room temperature. Amino acid synthons, two containing HYBA and two containing HYNIC, were synthesised to be incorporated into the peptide ‘nanogastrin’ for chemoselective labelling. These hydrazine containing peptides were then to be radiolabelled with [18F]fluorobenzaldehyde. Early indications are that this approach to radiolabelling works as theorised.