Radiolabeled Bicyclic Peptides with metal chelators as central structural scaffolds – Radio-BIPeps

The project aims to develop new radiopharmaceutical tools for theranostic in nuclear medicine, i.e. for therapeutic and diagnostic applications with a same molecular object. To ensure the specific delivery of the radionuclide to the tumor, the radiometal, that is confined in a chelator, must be coupled to a disease-specific targeting vector. Cyclic peptides are highly attractive as biovectors (advantageous pharmacokinetics, high penetration into tumor tissue, high metabolic stability and target affinity) but their potential for radiopharmaceutical development has not extensively been explored to date. The idea is to use metals polyazamacrocyclic chelators like tacn that will be incorporated in the bicyclic peptides in an innovative way in order to furnish original radiolabeled conjugates. To obtain important insights into the interplay between the metal chelator, tether(s), and cyclic peptide(s), a series of conjugates will be prepared and their biological properties assessed (receptor affinity and metabolic stability) in cell experiments. After further structural optimization, the biodistribution of the most promising candidates will then be assessed in small-animal experiments including PET imaging. The feasibility of this new approach will be demonstrated by following anticipated steps skillfully shared between the two partners: 1) chemical modifications of metal chelators for their subsequent incorporation in the peptides; 2) insertion of the chelators in the bicyclic peptides; 3) radiolabeling and characterization of non-radioactive metal complexes of bicyclic peptide conjugates; 4) in vitro characterization of radiopharmaceuticals; 5) preliminary in vivo evaluations of selected bicyclic peptide conjugates.