Bone lesion absorbed dose profiles in patients with metastatic prostate cancer treated with molecular radiotherapy

OBJECTIVE: The aim of this study was to calculate the range of absorbed doses that could potentially be delivered by a variety of radiopharmaceuticals and typical fixed administered activities used for bone pain palliation in a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). The methodology for the extrapolation of the biodistribution, pharmacokinetics and absorbed doses from a given to an alternative radiopharmaceutical is presented. METHODS: Sequential single photon emission CT images from 22 patients treated with 5 GBq of (186)Re-HEDP were used to extrapolate the time–activity curves for various radiopharmaceuticals. Cumulated activity distributions for the delivered and extrapolated treatment plans were converted into absorbed dose distributions using the convolution dosimetry method. The lesion absorbed doses obtained for the different treatments were compared using the patient population distributions and cumulative dose–volume histograms. RESULTS: The median lesion absorbed doses across the patient cohort ranged from 2.7 Gy (range: 0.6–11.8 Gy) for 1100 MBq of (166)Ho-DOTMP to 21.8 Gy (range: 4.5–117.6 Gy) for 150 MBq of (89)Sr-dichloride. (32)P-Na(3)PO(4), (153)Sm-EDTMP, (166)Ho-DOTMP, (177)Lu-EDTMP and (188)Re-HEDP would have delivered 41, 32, 85, 20 and 64% lower absorbed doses, for the typical administered activities as compared to (186)Re-HEDP, respectively, whilst (89)Sr-dichloride would have delivered 25% higher absorbed doses. CONCLUSION: For the patient cohort studied, a wide range of absorbed doses would have been delivered for typical administration protocols in mCRPC. The methodology presented has potential use for emerging theragnostic agents. ADVANCES IN KNOWLEDGE: The same patient cohort can receive a range of lesion absorbed doses from typical molecular radiotherapy treatments for patients with metastatic prostate cancer, highlighting the need to establish absorbed dose response relationships and to treat patients according to absorbed dose instead of using fixed administered activities.