The aim of this study is to develop a novel personalized post-surgical therapy concept using tailor-made Auger-e‒-emitting PSMA ligands. The proposed concept is thought to provide a specific class of prostate cancer patients, characterized by localized disease, but high risk of relapse after surgery, with a better long-term prognosis.
With this proposal we aim at achieving a critical step towards a personalized approach of prostate cancer treatment by means of PSMA-targeting using non-standard radionuclides for post-surgical eradication of surviving cancer cells. It is expected that after this PhD thesis, it is known (i) whether PSMA is a valid tumor target for this specific class of patients, (ii) whether it is possible to achieve PSMA targeting followed by shuttling the radioligand into the cellular nucleus and, (iii) whether Auger-e‒-emitting radionuclides would be more suited than pure β‒- particle emitters to effectively kill these cancer cells. Most importantly, it will be known (iv) whether post-surgical Auger-e‒ therapy can reduce the cases of relapse after removal of the primary tumor mass based on the in vitro/ex vivo and in vivo data obtained in diverse personalized preclinical models including organoids, tissue cultures and patient-derived xenograft (PDX)-models.
