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

«Radiation and Risk», 2023, vol. 32, No. 3, pp.134-142

DOI: 10.21870/0131-3878-2023-32-3-134-142

Authors

Matveev A.V. – Associate Prof., C. Sc., Phys.-Math. OmSMU. Contacts: 12 Lenin str., Omsk, Russia, 644099. Tel.: +79043251774; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Petriev V.M. – Head of Lab., D. Sc., Biol. A. Tsyb MRRC.
¹ Omsk State Medical University of the Ministry of Health of the Russian Federation, Omsk
² A. Tsyb MRRC, Obninsk

Abstract

Since the beginning of the XXI century, active research has begun on the development of funda-mentally new radiopharmaceutical drugs based on alpha-emitting maternal radionuclides for radionuclide therapy of microtumors 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 daugh-ter 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 ²²⁵Ac, injected into the blood as part of its chloride ²²⁵AcCl₃, and the osteotropic preparation ²²⁵Ac-KHEDP (monokalium salt of hydroxyethylidendiphosphonic acid) labeled with it were selected. Quantitative data on the bio-distribution of ²²⁵Ac-KHEDP and ²²⁵AcCl₃ in the body of intact mice were used to identify the necessary parameters. Calculations of the dosimetric characteristics of two ²²⁵Ac-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 ²²⁵Ac-KHEDP, all radiation loads on the blood are approximately 2.5 times less compared to ²²⁵AcCl₃, which is explained by the higher blood clearance value for ²²⁵Ac-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.

Key words
dosimetry, actinium-225, radiopharmaceutical, radionuclide, compartment modeling, nuclear medicine, absorbed doses, radioactivity.

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