Iain Murray1,2, Sarah J Chittenden3,4, Ana M Denis-Bacelar3,4, Cecilia Hindorf3,4,5, Christopher C Parker6, Sue Chua7, Glenn D Flux3,4. 1. Joint Department of Physics, Royal Marsden NHS Foundation Trust, Downs Rd., Sutton, Surrey, SM2 5PT, UK. iain.murray@icr.ac.uk. 2. The Institute of Cancer Research, London, UK. iain.murray@icr.ac.uk. 3. Joint Department of Physics, Royal Marsden NHS Foundation Trust, Downs Rd., Sutton, Surrey, SM2 5PT, UK. 4. The Institute of Cancer Research, London, UK. 5. Department of Radiation Physics, Skåne University Hospital, Lund, Sweden. 6. Department of Urology, Royal Marsden NHS Foundation Trust, Sutton, UK. 7. Department of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Sutton, UK.
Abstract
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.
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.
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