Evaluation of the 223Ra-dichloride biodistribution models for the assessment of the doses from internal exposure

Prostate cancer is the most common men urogenital tumor. For most patients with the disseminated neoplastic process in the prostate after the hormonal therapy, the disease gradually progresses in the form of castration-resistant prostate cancer (mCRPC). The use of 223 Ra agents is aimed at the treatment of the bone lesions as part of palliative therapy. The physical properties of 223 Ra significantly complicate the require direct radiometry for patients with alpha emitters. Hence, the distribution of 223 Ra in the body should be evaluated based on the dedicated biodistribution models. The aim of this study was to review and analyze the existing approaches to the evaluation of the biodistribution of 223 Ra and its pharmaceutical forms ( 223 Ra-dichloride) for the further assessment of absorbed doses in radiosensitive organs and tissues. The study includes the mathematical models for the estimation of the absorbed doses in various organs and tissues of the body. A review of three different 223 Ra biodistribution models is presented: two ICRP models for occupational exposure and a model based on the results of an experimental assessment of 223 Ra distribution in patients with mCRPC. It was indicated that the latter model is in good agreement with the results of direct radiometry of patients. A significant drawback of all models is the simulation of the red bone marrow and bone surface as single chambers. During the radionuclide therapy, 223 Ra will specifically accumulate in bone metastases, instead of being evenly distributed in the skeleton. Hence, the use of any of the reviewed models will lead both to a significant overestimation of the absorbed dose in a healthy part of the bone surface and red bone marrow, and to an underestimation of the absorbed dose in bone metastases. Currently, this problem has not been solved. That requires the development of new improved models that consider the accumulation of 223 Ra in the healthy part of the skeleton and in skeletal metastases.