Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Ziel/Aim:

The synthesis of fluorine-18 labeled peptides with high affinity towards the EphB2 receptor and the evaluation as radiotracers for PET was described. This receptor is known to be overexpressed in various types of cancer. Thus, a peptide was applied with high affinity to the EphB2 receptor which is strongly constrained of the amino acid key sequence SNEW. Two novel bifunctional and bioorthogonal building blocks were evaluated. The labeling of the peptides was done using the Huisgen click approach.

Methodik/Methods:

Two labeling building blocks based on the piperazine skeleton with either alkyne or azide function were used and an automated module synthesis was evaluated. Further, it was found that the peptide SNEWILPRLPQH show a high affinity to EphB2. Thus, the C-terminus of the peptide was functionalized with alkyne or azide, to retain the high affinity which is constrained of the key sequence SNEW at the N-terminus.

Ergebnisse/Results:

The automated one-step radiosynthesis of two novel building blocks gave the desired piperazine derivatives [¹⁸F]AFP and [¹⁸F]BFP in radiochemical yields of 25-45% (d.c.) within 50 min and a high purity after convenient separation from [¹⁸F]F- and precursor using silica gel cardridges. Radiolabeling of several functionalized SNEW peptides under Click conditions pointed out that [¹⁸F]AFP is only suitable and yielded the radiofluorinated peptide in 10-15 % RCY (d.c.). A by-product was observed when the alkyne building block [¹⁸F]BFP was used due to the competing Glaser coupling. Finally, the peptide was prepared, radiolabeled and purified from the Cu with bispidine on SPPS. This is urgent, otherwise, aggreagtion of the peptide with Cu occur. Finally, the stability of the labeled SNEW peptide was investigated ex vivo showing >80% intact peptide after 1 h. Three more hydrophilic metabolites were observed not determined as [¹⁸F]F-.

Schlussfolgerungen/Conclusions:

With the SNEW peptides highly potent 18F-containing EphB2 inhibitors were found and the labeling on SPPS with [¹⁸F]AFP was successfully established.