In Vitro and In Vivo Studies of Boron Neutron Capture Therapy: Boron Uptake/Washout and Cell Death

Ferrari, C., Bakeine, J., Ballarini, F., Boninella, A., Bortolussi, S., Bruschi, P., Cansolino, L., Clerici, A. M., Coppola, A., Di Liberto, R., Dionigi, P., Protti, N., Stella, S., Zonta, A., Zonta, C. and Altieri, S. In Vitro and In Vivo Studies of Boron Neutron Capture Therapy: Boron Uptake/Washout and Cell Death. Radiat. Res. 175, 452-462 (2011). Boron neutron capture therapy (BNCT) is a binary radiotherapy based on thermal-neutron irradiation of cells enriched with B-10, which produces a particles and Li-7 ions of short range and high biological effectiveness. The selective uptake of boron by tumor cells is a crucial issue for BNCT, and studies of boron uptake and washout associated with cell survival studies can be of great help in developing clinical applications. In this work, boron uptake and washout were characterized both in vitro for the DHDK12TRb (DHD) rat colon carcinoma cell line and in vivo using rats bearing liver metastases from DUD cells. Despite a remarkable uptake, a large boron release was observed after removal of the boron-enriched medium from in vitro cell cultures. However, analysis of boron washout after rat liver perfusion in vivo did not show a significant boron release, suggesting that organ perfusion does not limit the therapeutic effectiveness of the treatment. The survival of boron-loaded cells exposed to thermal neutrons was also assessed; the results indicated that the removal of extracellular boron does not limit treatment effectiveness if adequate amounts of boron are delivered and if the cells are kept at low temperature. Cell survival was also investigated theoretically using a mechanistic model/Monte Carlo code originally developed for radiation-induced chromosome aberrations and extended here to cell death; good agreement between simulation outcomes and experimental data was obtained. (C) 2011 by Radiation Research Society