GRPR-targeted Theranostics for Cancer Management: New approaches to maximize therapeutic success

In nuclear medicine, molecular imaging utilizing tumor-targeting radioactive agents can be used to non-invasively identify cancer patients eligible for targeted radionuclide therapy based on a positive scan, a concept known as theranostics. The gastrin releasing peptide receptor (GRPR) is a promising target for such a theranostic application due to its overexpression in several frequently occurring cancers; a disease that is one of the leading causes of death in Europe. The aim of the research described in this thesis is to maximize the therapeutic success of GRPR-mediated theranostic approaches for cancer patients, including pretargeting and image-guided surgery as key strategies. More specifically, in this thesis we have 1) demonstrated the therapeutic efficacy and safety of the promising GRPR-targeting radiopharmaceutical [177Lu]Lu-NeoB treatment, 2) aided in the identification of PCa patient subgroups that may benefit from GRPR-mediated theranostics, 3) explored a NeoB-based pretargeting strategy, and 4) developed and characterized promising GRPR-targeting dual-modality probes.