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

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 prostate cancer. The methodology for the extrapolation of the biodistribution, pharmacokinetics and absorbed doses from a given to an alternative radiopharmaceutical is presented.

Sequential SPECT 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.

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.

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.

The British journal of radiology. 2018 Jan 02 [Epub ahead of print]

Ana M Denis-Bacelar, Sarah J Chittenden, V Ralph McCready, Antigoni Divoli, David P Dearnaley, Joe M O'Sullivan, Bernadette Johnson, Glenn D Flux

1 Chemical, Medical and Environmental Science Department, National Physical Laboratory, Teddington, UK., 2 Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK., 3 3Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, UK., 4 Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK., 5 Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.