Dynamics of formation of absorbed doses in the blood of laboratory animals from alpha-emitting radionuclides with successive decays

Since the beginning of the XXI century, active research has begun on the development of fundamentally new radiopharmaceutical drugs based on alpha-emitting maternal radionuclides for radionuclide therapy of micro-tumors and metastases. The main difficulty in assessing the absorbed doses of internal irradiation of such drugs is to take into account the radiation loads from all daughter radionuclides of sequential decay with alpha and beta transformations. The aim of the work is to develop a methodology for calculating the accumulated and total absorbed doses in the blood of laboratory animals from alpha-emitting radionuclides with successive decays within the framework of the compartment modeling method. To test the developed methodology and calculate the dosimetric characteristics, the free isotope Ac-225, injected into the blood as part of its chloride Ac-225Cl3, and the osteotropic preparation Ac-225-KHEDP (monokalium salt of hydroxyethylidendiphosphonic acid) labeled with it were selected. Quantitative data on the bio-distribution of Ac-225-KHEDP and Ac-225Cl3 in the body of intact mice were used to identify the necessary parameters. Calculations of the dosimetric characteristics of two Ac-225-labeled drugs in the blood of intact mice showed that the values of accumulated absorbed doses monotonically increase from the moment of drug administration, reaching their limit values equal to the total absorbed doses by about 300 hours. Alpha-emitting parent and daughter radionuclides make the main contribution to the values of total absorbed doses. The contribution of daughter beta-emitting radionuclides is significantly less, therefore, they can be ignored when preliminary estimates of the total absorbed doses are made. When using Ac-225-KHEDP, all radiation loads on the blood are approximately 2.5 times less compared to Ac-225Cl3, which is explained by the higher blood clearance value for Ac-225-KHEDP. The results obtained indicate the prospects for further studies of 225Ac-KHEDP and the possibility of its clinical application for the treatment of skeletal metastases.