Ligand engineering for theranostic applications

Targeted therapy of cancer is considered as promising alternative approach to conventional chemotherapy and radiotherapy. Recent advancements in biotechnology have significantly improved the identification of novel radiopharmaceuticals allowing for more accurate imaging and therapeutic targeting of epithelial tumors. The successful development of radiotracers critically depends on the selection and validation of the tumor-specific target structure, the technical approach employed for the identification of a target-specific ligand, and the evaluation and improvement of the binding properties and the pharmacokinetic profile of the ligand by biotechnological procedures or chemical modification, respectively. Employing rational design of a quinoline-based fibroblast activation protein inhibitor (FAPI) and ‘high-through put’ display technology using a sunflower trypsin inhibitor1-based peptide library, several FAPI derivatives and a novel αvβ6 integrin-binding peptide (SFITGv6) were identified. FAPI and SFITGv6 represent powerful radiopharmaceuticals for diagnostic imaging and/or endoradiotherapy of FAP- and αvβ6 integrin-expressing epithelial tumors, respectively.