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1998 ; 89
(12
): 1352-7
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Effect of electroporation on cell killing by boron neutron capture therapy using
borocaptate sodium (10B-BSH)
#MMPMID10081497
Ono K
; Kinashi Y
; Masunaga S
; Suzuki M
; Takagaki M
Jpn J Cancer Res
1998[Dec]; 89
(12
): 1352-7
PMID10081497
show ga
The cell membrane permeability of 10B-enriched borocaptate sodium (BSH) and the
extent to which BSH is accumulated in cells are controversial. To elucidate these
points and to enhance the accumulation of BSH in cells, the effect of
electroporation on boron neutron capture therapy (BNCT) using BSH was
investigated. The first group of SCCVII tumor cells was incubated in culture
medium with 10B-BSH or 10B-enriched boric acid, and exposed to neutrons from the
heavy water facility of the Kyoto University Reactor. More than 99% of neutrons
were thermal neutrons at flux base. The second group was pretreated with
electroporation in combination with 10B-BSH, and thereafter the cells were
irradiated with neutrons. The cell-killing effect of BNCT was measured by colony
formation assay. The surviving cell fraction decreased exponentially with neutron
fluence, and addition of BSH significantly enhanced the cell-killing effect of
NCT depending on 10B concentration and the preincubation time of cells in the
BSH-containing culture medium. The electroporation of cells with BSH markedly
enhanced the BNCT effect in comparison with that obtained with preincubation
alone. The effect of BSH-BNCT with electroporation was almost equal to that of
BNCT using 10B-boric acid at the same 10B concentration. The effect of BNCT on
cells pretreated with BSH and electroporation was not reduced by repeated washing
of the cells before neutron irradiation. Decrease of the effect of BSH-BNCT plus
electroporation with increase in the waiting time between the electroporation and
the neutron irradiation could be explained in terms of the extent of cell growth
during that time. These data suggest that BSH penetrates the cells slowly and
remains after washing. Electroporation can introduce BSH into the cells very
efficiently, and BSH thus introduced stays in the cells and is not lost in spite
of the intensive washing of the cells. Therefore, if electroporation is applied
to tumors after BSH injection, 10B would remain in the tumors but be cleared from
normal tissues, and selective accumulation of 10B in tumors will be achieved
after an appropriate waiting time.