Innovative radiolabelling strategies for CCK2R targeting

Molecular imaging plays an important role in personalized medicine and allows to monitor physiological processes using different imaging techniques. In nuclear medicine, radiolabelled substances that specifically dock to binding sites on the cancer cells are used for the visualization of tumour sites. One possible binding site present in various tumours, such as medullary thyroid carcinomas, is the cholecystokinin-2 receptor. The peptide hormone minigastrin binds specifically to this receptor. In this project, new radiolabelled minigastrin derivatives are being developed with focus on new radiopharmaceuticals that can be used for high sensitivity positron emission tomography (PET). Specific modifications are incorporated into the new minigastrin derivatives to protect them from rapid degradation by enzymes in the body. In addtion, the number of amino acids is reduced to optimize the pharmacokinetics. The applied chemical changes show potential to improve the biodistribution and tumour uptake, thus resulting in better imaging properties. Different radiolabelling strategies, such as complex formation with gallium-68 via the use of different ligands, as well as two different strategies of radiofluorination are also being investigated. The specific receptor binding of the new radiolabelled compounds will be evaluated in cell experiments. In addition, also other properties relevant for potential clinical use will be investigated. These studies require animal experiments in which the distribution of the radioactive compounds in the body and the imaging properties are studied using dedicated small animal cameras. The new radiolabelled minigastrin derivatives with improved stability and increased tumour uptake show high potential for clinical use in targeted cancer diagnosis. The research field of radiopharmacy will gain new knowledge from the newly investigated modifications and comparative studies with different radionuclides which will promote the development of other radioactive compounds starting from peptide hormones. The ultimate goal of the project is to develop a new radiopharmaceutical for clinical use in PET imaging of tumours presenting the cholecystokinin-2 receptor on the cell surface.