Whole-Body Diffusion-Weighted-MRI is emerging as an imaging response biomarker in metastatic bone disease. Documentation of mixed therapeutic response is a key recommendation of the Prostate Cancer Working Group as recognition of coexistence of mixed response to therapy and clinical benefit. Radium-223 has shown efficacy in prostate cancer patients with symptomatic bone metastases. Monitoring Radium-223 therapy efficacy treatment is challenging, as Radium-223 administration can be associated with flare in pain, PSA and Bone Scan. These pilot data demonstrate that Radium-223 administration is associated with an increase in bone metastases ADC values together with a mixed response pattern.