Comparative studies on the potential use of Lu-based radiopharmaceuticals for the palliative therapy of bone metastases.

In recent years, radionuclides like Lu have been considered promising material for the creation of therapeutic radiopharmaceuticals. With the therapeutic use of radiopharmaceuticals, the absorbed doses per tumor may exceed 10 Gy. It is extremely important that doses absorbed by healthy organs and tissues do not exceed the threshold for the incidence of deterministic effects. The potential use of the radionuclide lutetium-177 for the palliative treatment of pain in bone metastases is analyzed. The radionuclide Lu is a beta-emitting nuclide with a maximal energy of 0.49 MeV and a half-life of 6.6 days (161 h). Two therapeutic agents were considered: methylene diphosphonate (MDP) and ethylenediamine tetramethylene phosphonic acid (EDTMP). Both drugs contain phosphorus compounds in their composition, which ensures high tropism in bone tissue. For both drugs, biokinetic models of Lu's behavior in the human body are created. A number of studies have shown that the radiochemical stability of these drugs is about 99%: these calculations took into account the presence of a free Lu radionuclide in each solution. The absorbed doses in organs and tissues when using the radiopharmaceuticals Lu-MDP and Lu-EDTMP, as well as the currently used drugs Sm-EDTMP and SrCl, are compared. In order to assess the risk of the patient's exposure to a radiopharmaceutical, the absorbed doses are calculated for each organ where the radioactive label is mainly deposited: the kidneys, red bone marrow, liver and bone surface. The intensity of dose accumulation when using different drugs on the pathological focus is different. The drug Lu-MDP is faster than other drugs when it comes to the full realization of the expected dose; therefore, a therapeutic effect is achieved faster when it is used. The slowest absorbed dose accumulates when strontium chloride is used. To compare the effectiveness of preparations based on the Lu radionuclide, an analysis of the radiopharmaceuticals currently used for the palliative therapy of bone metastases (SrCl and Sm-EDTMP) was performed. For Sr, the most vulnerable organs are the kidneys, red bone marrow and liver, while for Sm-EDTMP, red marrow bone is most vulnerable. For radiopharmaceuticals based on the Lu radionuclide, the most vulnerable organs are the kidneys, liver and red bone marrow. This proves the effectiveness of the Lu-MDP and Lu-EDTMP radiopharmaceuticals. According to the results of the calculations, Lu-EDTMP and Lu-MDP demonstrate the best results for the palliative therapy of bone metastases.