The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer

Purpose The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of Ra-223-dichloride, to assess the relationship between those doses and corresponding F-18-fluoride uptake and to assess the potential of quantitative F-18-fluoride imaging to predict response to treatment. Methods Five patients received two intravenous injections of Ra-223-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of Ra-223 in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial Ra-223 scans. PET/CT imaging using F-18-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline. Results Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5-11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in 18F- fluoride uptake was demonstrated (r(2) = 0.52). A log-linear relationship was demonstrated (r(2) = 0.77) between baseline measurements of F-18-fluoride uptake prior to Ra-223-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both Ra-223 and F-18- fluoride uptake in lesions (r = 0.75) as well as between Ra-223 absorbed dose and F-18-fluoride uptake (r = 0.96). Conclusions There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between Ra-223 lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of 18F- fluoride in bone metastases is significantly correlated with corresponding uptake of Ra-223, the associated Ra-223 absorbed dose and subsequent lesion response to treatment.