Dynamics of formation of absorbed doses in organs and tissues of laboratory animals from alpha-emitting radionuclides with successive decays

The main problem in the assessment of the absorbed doses of internal irradiation of drugs marked with alpha-emitting radionuclides 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 accumulated and total absorbed doses in organs and tissues of laboratory animals from alpha-emitting radionuclides with successive decays within the framework of the pharmacokinetic modeling method. To test the developed technique and calculate the dosimetric characteristics, the actinium-225-labeled drug Ac-225-PSMA (prostate-specific membrane antigen) was selected, intended for targeted peptide-receptor radionuclide therapy of prostate cancer. To identify the necessary parameters, quantitative data on the bio-distribution of Ac-225-PSMA in the body of BALB/c nu/nu (nude) mice with subcutaneously implanted malignant prostate tumor (22Rv1) were used. Calculations have shown that the values of accumulated absorbed doses in organs and tissues increase monotonously from the moment the drug is injected into the blood, reaching their maximum values over a period of time equal to five effective half-lives of the drug from the corresponding organ or tissue. The main contribution to the values of total absorbed doses is provided by alpha-emitting parent and daughter radionuclides. The contribution of daughter beta-emitting radionuclides is significantly less. Therefore, they can be ignored in preliminary estimates of absorbed doses. It was revealed that Ac-225-PSMA, having a high clearance, is rapidly excreted from the blood mainly by the kidneys. At the same time, the total absorbed dose in the tumor tissue of the prostate gland exceeds several times the total absorbed doses in other organs and tissues, except the liver and kidneys. The results obtained indicate the prospects for further studies of Ac-225-PSMA and the possibility of its clinical application for radionuclide therapy of prostate cancer.