Due to the increasing number of therapies and wide variety in response to treatment of patients with metastatic castration resistant prostate cancer (mCRPC), reliable biomarkers for response prediction and evaluation are needed. In this thesis, we investigated the value of novel PET imaging, large scale genomics and liquid biopsies as biomarkers for patients with mCRPC. Overall, the investigated biomarkers showed promising results, and could be used to improve treatment guidance after prospective validation in larger patient cohorts. In addition, we gained detailed insight in the response to radium-223, which improved our understanding of the working mechanism and possibilities for application of radium-223