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

Abstract

Purpose The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of 223 Ra-dichloride, to assess the relationship between those doses and corresponding 18 F-fluoride uptake and to assess the potential of quantitative 18 F-fluoride imaging to predict response to treatment.Methods Five patients received two intravenous injections of 223 Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of 223 Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial 223 Ra scans. PET/CT imaging using 18 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 18 F-fluoride uptake was demonstrated (r 2 = 0.52). A log-linear relationship was demonstrated (r 2 = 0.77) between baseline measurements of 18 F-fluoride uptake prior to 223 Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both 223 Ra and 18 F-fluoride uptake in lesions (r = 0.75) as well as between 223 Ra absorbed dose and 18 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 223 Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of 18 F-fluoride in bone metastases is significantly correlated with corresponding uptake of 223 Ra, the associated 223 Ra absorbed dose and subsequent lesion response to treatment.