Rationale Radiolabelled bisphosphonates such as 99mTc-DPD typically show intense uptake in skeletal metastases from metastatic castration resistant prostate cancer (mCRPC). Extensive bone involvement is regarded a risk factor for mCRPC patients treated with 223Ra-radiumdichloride (223Ra). Aim of this study was to quantify 99mTc-DPD uptake by means of SPECT/CT prior to 223Ra and compare results to the feasibility of treatment and overall survival (OS). Methods 60 consecutive mCRPC patients were prospectively included into this study. SPECT/CTs of the central skeleton covering the scull to mid-femoral level were carried out before the first cycle of 223Ra. The bone compartment was defined by means of low-dose CT. Emission data were corrected for scatter, attenuation and decay supplemented by resolution recovery using dedicated software. The Kaplan-Meier estimator, U-Test and Cox regression analysis were employed for statistics. Results Total 99mTc-DPD uptake of the central skeleton varied between 11-56 percent of injected dose (%ID) or 1.8-10.5 %ID/1000 ml bone volume (%ID/L). SUVmean ranged from 1.9-7.4 while SUVmax range was 18-248. Patients unable to complete 223Ra treatment due to progression a/o. cytopenia (n=23) showed significantly higher uptake (31.9 vs. 25.4%ID; 6.0 vs 4.7x %ID/L, P <0.02). OS after 223Ra (median: 15.2 months) was reduced to 7.3 months in case of skeletal uptake ≥26 %ID as compared to 30.8 months if <26 %ID (p=0.008). Similar results were obtained for %ID/L and SUVmean. SUVmax was not correlated to survival. %ID/L was identified as an independent prognostic factor for OS (Hazard ratio 1.381 per unit) along with number of previous treatment lines. Conclusion Quantitative SPECT/CT of bone scans performed at baseline is prognostic for survival of mCRPC patients treated with 223Ra.