Radioligand Therapy (RLT) has fast become an established approach in the fight against cancer. Previously, several PARP inhibitors coupled with different radionuclides have been developed by us and others, for imaging and RLT. However, the comparative efficacy and radiobiological effect of these compounds has not been systematically explored. We do not fully grasp the biological effects that are triggered, or which emitters are more useful in RLT with intracellular targets. Should this be accomplished, together with a more refined understanding of radiation dose, dose rate, and radiation dosimetry, then patient selection, and the efficacy of RLT will be much improved. Therefore, we propose a systematic comparison of PARP inhibitors labelled with (211At, 225Ac), beta (161Tb, 177Lu), or Auger-electron emitting radionuclides (123I, 125I, 161Tb). Our eventual goal is to identify which offers the greatest radiotoxicity with the fewest undesired side effects. We will synthesise a series of radiolabelled versions of the PARP inhibitor, olaparib. Subsequently, we will expose a panel of human cancer cell lines, expressing different PARP levels, to these radiolabelled PARP inhibitors. The objective is to determine how these compounds differently affect cell survival and identify which signalling pathways are triggered by them. In a follow-up project, we will also test their efficacy in vivo and determine normal tissue toxicity. With this project we aim to unveil new strategies to develop RLT and explore the differences between different radionuclides, using the same vector. This will undoubtedly open new pathways for optimised RLT selection which will have a significant impact by enhancing the selection of RLT drugs, establishing the foundational knowledge for RLT development, and advancing the development of new RLT drugs that could eventually be integrated into patient care.