The potential of Ra and F-fluoride imaging to predict bone lesion response to treatment with Ra-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-dichloride, to assess the relationship between those doses and corresponding F-fluoride uptake and to assess the potential of quantitative F-fluoride imaging to predict response to treatment.

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