PURPOSE: The cell membrane permeability of borocaptate (10B-BSH) and its extent of accumulation in cells are controversial. This study was performed to elucidate these points. METHODS AND MATERIALS: Two different treatments were applied to SCCVII tumor cells. The first group of tumor cells was incubated in culture medium with 10B-BSH or 10B-enriched boric acid, and was exposed to neutrons from the heavy water facility of the Kyoto University Reactor (KUR). More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated by electroporation in combination with 10B-BSH, and thereafter the cells were irradiated with neutrons. The cell killing effects of boron neutron capture therapy (BNCT) using BSH were investigated by colony formation assay. RESULTS: Surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell killing effect of neutron capture therapy (NCT) depending on 10B concentration. The effect of BSH-BNCT also increased with preincubation time of cells in the medium containing BSH. The electroporation of cells with BSH at 10 ppm 10B markedly enhanced BSH-BNCT effects in comparison with that of preincubation alone. The effect of BSH-BNCT with electroporation was equal to that of BNCT using 10B-boric acid at a same 10B concentration (10 ppm). CONCLUSIONS: BSH is suggested to penetrate the cells slowly and remained after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH stays in the cells and is not lost by washing. Therefore, if electroporation is applied to tumors after BSH injection, 10B remains in tumors but is cleared from normal tissues, and selective accumulation of 10B in tumors will be achieved after an adequate waiting time.
PURPOSE: The cell membrane permeability of borocaptate (10B-BSH) and its extent of accumulation in cells are controversial. This study was performed to elucidate these points. METHODS AND MATERIALS: Two different treatments were applied to SCCVII tumor cells. The first group of tumor cells was incubated in culture medium with 10B-BSH or 10B-enriched boric acid, and was exposed to neutrons from the heavy water facility of the Kyoto University Reactor (KUR). More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated by electroporation in combination with 10B-BSH, and thereafter the cells were irradiated with neutrons. The cell killing effects of boron neutron capture therapy (BNCT) using BSH were investigated by colony formation assay. RESULTS: Surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell killing effect of neutron capture therapy (NCT) depending on 10B concentration. The effect of BSH-BNCT also increased with preincubation time of cells in the medium containing BSH. The electroporation of cells with BSH at 10 ppm 10B markedly enhanced BSH-BNCT effects in comparison with that of preincubation alone. The effect of BSH-BNCT with electroporation was equal to that of BNCT using 10B-boric acid at a same 10B concentration (10 ppm). CONCLUSIONS:BSH is suggested to penetrate the cells slowly and remained after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH stays in the cells and is not lost by washing. Therefore, if electroporation is applied to tumors after BSH injection, 10B remains in tumors but is cleared from normal tissues, and selective accumulation of 10B in tumors will be achieved after an adequate waiting time.
Authors: Marcela A Garabalino; Nahuel Olaiz; Agustina Portu; Gisela Saint Martin; Silvia I Thorp; Emiliano C C Pozzi; Paula Curotto; María E Itoiz; Andrea Monti Hughes; Lucas L Colombo; David W Nigg; Verónica A Trivillin; Guillermo Marshall; Amanda E Schwint Journal: Radiat Environ Biophys Date: 2019-05-23 Impact factor: 1.925