This thesis deals with the design of ¹⁸F- and ⁶⁸Ga-labelled positron emission tomography (PET) tracers and the development of technologies that enable faster and simpler preparation with high specific radioactivity. Techniques like microwave heating and reducing the concentrations of the precursor were investigated with this perspective. A few applications were explored using molecular design perspectives.

A nucleophilic ¹⁸F-labelling strategy using perfluoro-containing leaving groups was explored. We observed that [¹⁸F]fluoride was interacting with the perfluoro alkyl chains of the substrate, preventing the nucleophilic substitution from taking place. When a perfluoroaryl group was instead used in the leaving group, the substitution took place and purification by fluorous solid-phase extraction was possible.

¹⁸F-Labelled analogues of the monoamine oxidase-A inhibitor harmine were prepared by one-step nucleophilic fluorinations and evaluated by in vitro autoradiography, showing high specific binding.

Biotin analogues labelled with ¹⁸F and ⁶⁸Ga were prepared and their binding to avidin evaluated. All analogues retained their binding ability and will be further evaluated in transplantation models with avidin-coated islets of Langerhans.

Peptide design perspectives were used in some examples where the Arg-Gly-Asp (RGD) sequence and a single-chain version of vascular endothelial growth factor (VEGF) protein functionalized with 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) or 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA) as chelators were labelled with ⁶⁸Ga. The RGD motif and VEGF have high affinity for, respectively, α_vβ₃ integrin and VEGFR-2 receptor that are overexpressed in angiogenesis process. The ⁶⁸Ga-labelled scVEGF maintained its functional activity in vitro.

A polypeptide conjugate containing phosphocholine, which has affinity for the C-reactive protein released during the inflammatory process, was labelled with ⁶⁸Ga for the development of an imaging agent for inflammation in vivo.

Finally [¹⁸F]/¹⁹F exchange in fluorine-containing compounds was studied in order to investigate whether the exchange reaction can be of practical use for labelling.