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 ²²³Ra-dichloride, to assess the relationship between those doses and corresponding ¹⁸F-fluoride uptake and to assess the potential of quantitative ¹⁸F-fluoride imaging to predict response to treatment. Methods: Five patients received two intravenous injections of ²²³Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of ²²³Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial ²²³Ra scans. PET/CT imaging using ¹⁸F-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 (r² = 0.52). A log-linear relationship was demonstrated (r² = 0.77) between baseline measurements of ¹⁸F-fluoride uptake prior to ²²³Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both ²²³Ra and ¹⁸F-fluoride uptake in lesions (r = 0.75) as well as between ²²³Ra absorbed dose and ¹⁸F-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 ²²³Ra 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 ²²³Ra, the associated ²²³Ra absorbed dose and subsequent lesion response to treatment.