Two α-amino acids labelled with 18F, 2-[18F]fluoro-L-tyrosine and 6-[18F]fluoro-L-dopa, are routinely produced at the CRC for PET clinical investigation in oncology and neurology. The first one is a tracer for the in vivo quantitative assessment of cerebral protein synthesis (tumor seeking agent) and the second one is a tracer for in vivo cerebral studies of presynaptic dopaminergic functions. Routine production of these two α-amino acids has been conducted in our laboratory, using a nucleophilic, multistep radiosynthesis approach. The no-carrier-added (nca) [18F]fluoride, which is available in large amounts from proton irradiation of 18O-enriched water in a cyclotron, allows the labelling of benzaldehyde derivatives by the substitution of a good leaving group. The synthesis of [18F]fluorobenzyl bromide derivative by reduction and bromination with gaseous HBr followed by the enantioselective alkylation under Phase Transfer Catalysis (PTC) of a benzophenone imine provides the protected radiopharmaceutical which is hydrolysed and purified by HPLC.
Due to the fact that gaseous HBr is quite cumbersome to handle and that its complete automation is difficult, the first goal of our work is to evaluate new methods for the synthesis of the [18F]fluorobenzyl bromide derivatives starting from the labelled benzaldehyde derivatives. In order to propose a radiochemical reaction which can be easily automated, we have evaluated different reactions on solid (and non solid) supported reagents. Five reagents were tested. N-piperidinoaminomethylpolystyrene hydrobromide resin gives the the [18F]fluorobenzyl bromide derivatives as unique products in good yields.
In the second part of our work, a new approach for the labelling of peptides from the key intermediate p-[18F]fluorobenzyl bromide has been evaluated using the concept of click chemistry. 1,3-dipolar cycloaddition provides fast access to a large number of five-membered heterocycles. We have used this cycloaddition to label protected p-ethynyl-L-phenylalanine with p-[18F]fluorobenzyl azide. This interesting labelling method will be applied to the labelling of a peptide containing this α-amino acid residue.