Development of novel radiotracers targeting oncofetal proteins for the diagnosis and therapy of tumors

• Applicant: Professor Dr. Uwe Haberkorn
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Pharmacy
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 523936964

Oncofetal proteins are highly expressed during the development of fetal tissues as well as in tumor cells or tumor stem cells. In contrast, in human adult tissues these proteins disappear or are only weakly expressed. Therefore, these structures are ideal targets for the development of carrier molecules which selectively transport cytotoxic and immunomodulatory molecules or also radioactive isotopes in tumor tissues without affecting normal tissues. The goals of this project are 1. identification of ligands (peptides or sybodies) with specific binding to the oncofetal proteins 5T4, Cripto-1 and ROR1 using Phage- and/or Ribosome-Display against recombinant target proteins or cell lines with recombinant or constitutive expression of the targets. 2. Evaluation of the ligands in vitro und in vivo: after radiolabelling of the ligands the binding to recombinant proteins, target-positive and -negative cells is measured as well as the internalisation and the efflux rate. Affinity is determined in competition experiments and using plasmon surface resonance spectroscopy. Stability will be measured in human serum. If needed an affinity maturation is done by randomisation of the amino acid sequences. The pharmacokinetic properties of the optimized ligands are investigated after radiolabelling in tumor-bearing mice by biodistribution experiments and small animal SPECT and/ or -PET Imaging.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Verena Böhmer