Calculation of pharmacokinetic and dosimetric characteristics of albumin microspheres labeled with Re-188 for various routes of administration

Radiopharmaceutical drugs labeled with 188Re are widely used in bone metastases, hepatocellular carcinoma and metastatic liver damage, skin tumors, for the treatment of keloid lesions, rheumatoid arthritis and synovitis. New therapeutic radiopharmaceutical drugs with Re-188 are also currently being developed. Human serum albumin microspheres (HSA) are unique carriers for the selective and controlled radionuclide delivery to malignant tumors. The aim of the work is to develop a chamber mathematical model of the kinetics of Re-188 labeled HSA (Re-188-HSA) in laboratory animals with various routes of administration and calculate the pharmacokinetic and dosimetric characteristics of this drug based on it. The studies were carried out on outbred white mice and inbred C57BL/6 mice with transplanted Lewis adenocarcinoma after intravenous, intramuscular and intratumoral administration. The object of the study is Re-188-HSA with a diameter of 10-20 microns. The kinetic parameters of the model were identified using experimental data on the biodistribution of Re-188-HSA in mouse organs and tissues. Calculations of the pharmacokinetic and dosimetric characteristics of Re-188-HSA in laboratory animals were based on the identified kinetic parameters. The simulation results showed that the pharmacokinetic and dosimetric characteristics of Re-188-HSA in the body significantly depend on the administration route. The highest concentration of 188Re-HSA in organs and tissues with maximum accumulation in the lungs was observed after intravenous administration. After intramuscular or intratumoral administration the concentration of Re-188-HSA in organs and tissues was significantly lower, and the maximum concentration remained in the injection chamber for a long time. An increased accumulation of Re-188-HSA in the thyroid gland was also detected after all routes of admi-nistration. The maximum values of absorbed doses were obtained in the lung chamber after intravenous administration, in the thigh muscle chamber after intramuscular administration, and in the tumor chamber after intratumoral administration. The obtained results can be used to evaluate the Re-188-HSA potential for tumor therapy after intravascular or intratumoral administration.