RESUMO
The interaction of mercaptoundecahydrododecaborate (B12H11SH2-, BSH) with phosphatidylcholine was investigated in this study in order to illuminate possible uptake mechanisms of BSH in tumor cells. BSH has been used clinically in Japan as a boron containing agent in patients with malignant brain tumors for boron neutron capture therapy (BNCT). After infusion, BSH accumulates selectively in tumor tissue. Little is known for the mechanism of boron uptake to tumor cells. Fourier transform infrared (FTIR) spectrometry was used to quantify BSH (at wavenumber 2490 cm-1) and phosphatidylcholine (at wavenumber 2850-2970 cm-1). After extraction into carbon tetrachloride (CCl4), we could find an absorbance maximum at 2490 cm-1 as a B-H band in the mixture of BSH with phosphatidylcholine, which is attributed to a BSH-phosphatidylcholine complex, which could dissolve well in CCl4. The molar ratio of BSH to phosphatidylcholine in the CCl4 solution was at most one mole of BSH to two moles of phosphatidylcholine independent of the excess BSH. The doubly negatively charged BSH can interact with two phosphatidylcholine molecules through their singly positively charged choline residues. These ion pairs could be responsible for membrane binding and penetration, and for cell internalization.
Assuntos
Boroidretos/metabolismo , Boro , Terapia por Captura de Nêutron , Fosfatidilcolinas/metabolismo , Compostos de Sulfidrila/metabolismo , Boroidretos/química , Boro/análise , Calibragem , Glioma/radioterapia , Humanos , Fosfatidilcolinas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Compostos de Sulfidrila/químicaRESUMO
To determine binding and distribution of Na2B12H11SH (BSH) in glioma tissue in case of boron neutron capture therapy, an antibody to this compound was produced and used in immunohistochemical investigations. It is possible to trace BSH in immunohistochemistry, because BSH is firmly bound to the glioma tissue. The antibody against BSH is specific for that antigen, as tumor tissue from patients without BSH administration did not stain. In areas of healthy brain from BSH infused patients, no staining of tissue was detectable. In tumor tissues, BSH is presenting as a strong staining in cytoplasm and nucleus areas.