Abstract
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 186Re-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 166Ho-DOTMP to 21.8 Gy (range: 4.5–117.6 Gy) for 150 MBq of 89Sr-dichloride. 32P-Na3PO4, 153Sm-EDTMP, 166Ho-DOTMP, 177Lu-EDTMP and 188Re-HEDP would have delivered 41, 32, 85, 20 and 64% lower absorbed doses, for the typical administered activities as compared to 186Re-HEDP, respectively, whilst 89Sr-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.
Highlights
Prostate cancer is the most common cancer in males in the UK (2014), accounting for 26% of all new cancer diagnoses in males.[1]
Effective treatment is primarily palliative and disseminated bone metastases are often managed with molecular radiotherapy (MRT) towards the latter stages of the disease
The absorbed dose profiles fitted to log-normal distributions delivered by 186Re-HEDP and extrapolated for the MRT treatment plans in Table 1 are shown in Figure 2a and Figure 2b–g, respectively
Summary
Prostate cancer is the most common cancer in males in the UK (2014), accounting for 26% of all new cancer diagnoses in males.[1] Androgen deprivation therapy is the primary treatment for patients with metastatic prostate cancer, the disease eventually progresses to the castration-resistant stage. Effective treatment is primarily palliative and disseminated bone metastases are often managed with molecular radiotherapy (MRT) towards the latter stages of the disease. A wide range of radiopharmaceuticals are available for bone pain palliation in patients with metastatic castration-resistant prostate cancer (mCRPC). These include bone-seeking calcium-analogues such as 89Sr-dichloride and 223Ra-dichloride and phosphates such as 153Sm-EDTMP, 186Re-HEDP and 188Re-HEDP.[2,3] More recently, newly emerging radiolabelled prostate-specific
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