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

Boron neutron capture therapy (BNCT) is a binary radiotherapy
based on thermal-neutron irradiation of cells enriched
with 10B, which produces a particles and 7Li 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 DHD 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 radiationinduced
chromosome aberrations and extended here to cell
death; good agreement between simulation outcomes and
experimental data was obtained.