Study of Lithium Biodistribution and Nephrotoxicity in Skin Melanoma Mice Model: The First Step towards Implementing Lithium Neutron Capture Therapy

Abstract

Boron neutron capture therapy (BNCT) is one of the promising treatment methods for malignant melanoma. The main issue of this technology is the insufficient selectivity of 10B accumulation in tumor cells. As a result of the neutron absorption by boron, an 84% energy release occurred within the cell by the nuclear reaction 10B (n, α)7Li, which lead to tumor cell death. The use of lithium instead of boron brings a new unique opportunity—local 100% energy release—since all products of the 6Li (n, α)3H reaction have high linear energy transfer characteristics. The aim of this study was to determine the concentrations of Li in the tumor, skin, blood, brain and kidney in experimental animals with B16 melanoma and to analyze the potential Li toxicity after lithium carbonate administration at single doses of 300 and 400 mg/kg. Lithium carbonate was chosen since there is a long-term experience of its use in clinical practice for the treatment of psychiatric disorders. The inductively coupled plasma atomic emission spectrometry was used to evaluate Li concentrations in tissue samples. The accumulation efficiency of Li in the tumor was the highest at a time point of 30 min (22.4 µg/g; at a dose of 400 mg/kg). Despite the high lithium accumulation in the kidneys, the pathological changes in kidney tissues were not found. Thus, lithium may actually be used for the Li-NCT development and future studies can be conducted using 6Li and following irradiation of tumor cells using the schemes of lithium administration tested in this work.

Keywords

• skin melanoma
• lithium carbonate
• kidney
• toxicity
• lithium neutron capture therapy