Calculation of the dosimetric characteristics of the radiopharmaceutical “¹⁸⁸re-albumin microspheres” in the body of mice based on pharmacokinetic modeling

Abstract

Purpose. Development of a compartment mathematical model of the kinetics of the radiopharmaceutical “188Re-albumin microspheres” in the body of intact mice and calculation on its basis of the dosimetric characteristics of this drug – accumulated and total absorbed doses. Material and methods. The objects of the study were serum albumin microspheres labeled with rhenium-188 with a diameter of 10−20 microns and the comparison drug Na188ReO4. Experimental pharmacokinetic data were obtained on mongrel white mice. The compartment model includes a central blood compartment and peripheral compartments of the lungs, thyroid gland, stomach, spleen, liver and kidneys. Identification of the kinetic parameters of the model (transport constants) was performed using experimental data. The pharmacokinetic and dosimetric characteristics of radiopharmaceuticals in mice were calculated based on the identified values of the transport constants of the model. Results. The compartment mathematical model of the kinetics of 188Re-albumin microspheres in the body of intact mice has been developed in accordance with experimental conditions. The radiopharmaceutical “188Re-albumin microspheres” has high stability in vivo, selectively accumulates in the lungs. Its increased accumulation in the compartments of the liver and spleen was also revealed, which may be due to the partial disintegration of the deposited 188Re-albumin microspheres in the lung tissue as the protein microspheres resorbed. This drug is excreted from the blood mainly by the kidneys. The blood clearance value for it is about 8 times higher, and the radiation load on the blood is less, compared with Na188ReO4. 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 equal to the total absorbed doses by about 80 hours. The maximum values of absorbed doses were obtained in the lung compartment, which reflects the tropicity of 188Re-albumin microspheres to this organ. Conclusion. The obtained simulation results allow us to consider the radiopharmaceutical “188Re-albumin microspheres” as promising for radionuclide therapy of tumors of different localization with intravascular administration.