Comparative studies on the potential use of 177Lu-based radiopharmaceuticals for the palliative therapy of bone metastases

Abstract

Purpose: In recent years, radionuclides like ¹⁷⁷Lu 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.Materials and methods: The potential use of the radionuclide lutetium-177 for the palliative treatment of pain in bone metastases is analyzed. The radionuclide ¹⁷⁷Lu 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 ¹⁷⁷Lu'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 ¹⁷⁷Lu radionuclide in each solution. The absorbed doses in organs and tissues when using the radiopharmaceuticals ¹⁷⁷Lu-MDP and ¹⁷⁷Lu-EDTMP, as well as the currently used drugs ¹⁵³Sm-EDTMP and ⁸⁹SrCl₂, 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.Results: The intensity of dose accumulation when using different drugs on the pathological focus is different. The drug ¹⁷⁷Lu-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 ¹⁷⁷Lu radionuclide, an analysis of the radiopharmaceuticals currently used for the palliative therapy of bone metastases (⁸⁹SrCl₂ and ¹⁵³Sm-EDTMP) was performed. For ⁸⁹Sr, the most vulnerable organs are the kidneys, red bone marrow and liver, while for ¹⁵³Sm-EDTMP, red marrow bone is most vulnerable. For radiopharmaceuticals based on the ¹⁷⁷Lu radionuclide, the most vulnerable organs are the kidneys, liver and red bone marrow. This proves the effectiveness of the ¹⁷⁷Lu-MDP and ¹⁷⁷Lu-EDTMP radiopharmaceuticals.Conclusions: According to the results of the calculations, ¹⁷⁷Lu-EDTMP and ¹⁷⁷Lu-MDP demonstrate the best results for the palliative therapy of bone metastases.

Keywords: 177Lu; 177Lu-EDTMP; 177Lu-MDP; palliative therapy of bone metastases.