Optimization of boron determination with ICP-MS for boron neutron capture therapy (BNCT) studies in vitro: Masterproef ingediend tot het bekomen van de graad van Master in de Chemie

Boron neutron capture therapy (BNCT) is a cancer treatment under development. In this type of therapy, a nuclear reaction is employed to kill cancer cells. When boron-10 is irradiated with thermal neutrons, highly reactive alpha particles and lithium-7 nuclei are produced, both having a very short path length. When boron-10 is selectively internalized into malignant cells, the reactive nuclei will selectively kill the malignant cells after irradiation with thermal neutrons. Research into development of new and more efficient boron-containing compounds is an important aspect of state-of-the-art innovation in this field. Evaluation of new BNCT boron carrier compounds involves in vitro experiments. The aim of this research is the development of a method for the determination of boron in cells exposed to boron-containing molecules in vitro. For the quantitative determination of boron, inductively coupled plasma mass spectrometry (ICP-MS) was used. Prior to ICP-MS analysis, cells had to be digested in such a way to completely remove the carbon matrix, fully recover boron and prevent contamination with boron from external sources. A final optimized sample preparation method for cell cultured combined closed vessel hotplate-assisted acid digestion and UV digestion. In this way, low carbon contents (< LOD, 5 mg/L), low detection limits for boron (0.4 µg/L) and full boron recoveries (100 %) could be obtained. Employing this method, it was possible to quantitatively determine associated boron in cells after exposure to two BNCT compounds. The most efficient compound, L-BPA (4-borono-L-phenylalanine), resulted in an uptake of 1.26 ± 0.10 x 109 boron atoms/cell.