New bifunctional chelates for use in positron emission tomography

This project has focussed on synthesising a range of bifunctional chelators (BFCs) for use in nuclear medicine, in particular positron emission tomography (PET). When such BFCs are complexed to a M(III) ion the overall charge on the complex varies between -1 and -3; this is expected to affect the renal clearance and biodistribution of these complexes.;A range of novel BFCs were produced; the synthesis of each requiring the use of new di-ester pendant arms. The BFCs were coupled to a range of moieties, including a patented biologically active peptide designed to locate at the site of angiogenesis, in order to allow the imaging of tumours to take place. The ultimate aim of the project was to couple the biologically active peptide to a tert-butyl deprotected BFC. This was achieved using various methodologies and reagents. The solution behaviour of the corresponding Eu(III) complex was studied. The hydration state of the peptide-coupled BFC was found to be q = 1, with 1 H NMR spectroscopy indicating a 4:1 mixture of square antiprismatic (SAP) : twisted square antiprismatic (TSAP) geometric isomers in solution.;Complexes of Ga(III), Eu(III), Y(III) and In(III) were synthesised with various benzylamine and N-Benzoyl-Gly-Lys coupled and tert-butyl protected BFCs. These were studied by 1H NMR and fluorescence spectroscopy where possible to provide an insight into their solution behaviour. Luminescent lifetime measurements indicated that the hydration state of all Eu(III) complexes was q = 1, indicating an 8-coordinate complex (with respect to ligand) with the ninth site occupied by a water. 1H NMR spectroscopy revealed the predominant geometric isomer in solution to be SAP, usually with a 4 : 1 ratio of SAP:TSAP. Selected benzylamine and N-Benzoly-Gly-Lys coupled BFCs were radiolabelled with 68Ga, using microwave heating for 1 min in order to illustrate their potential use in PET. This proved to be a superior method of radiolabelling on a small scale when compared to conventional heating.