o-
Carboranylalanine (B10H10C2CH2CHNH2COOH) is a carborane-containing
amino acid, which has been synthesized as a potential capture agent for
boron neutron capture therapy (BNCT) of
cancer. The purpose of the present study was to develop a rational approach for the in vitro and in vivo evaluation of
boron containing compounds that possibly might be used for BNCT. The in vitro uptake of
carboranylalanine (CBA) was evaluated using two cell lines, the human
melanoma MRA 27, and the murine
Harding-Passey melanoma. Uptake of CBA by MRA 27 cells ranged from 135-551 micrograms B/10(9) cells following 3 hrs incubation with medium containing 100-113 micrograms B/ml and was not reduced by exposing the
tumor cells to either
rotenone, an inhibitor of electron transport, or by culturing them at ambient temperature (approximately 22 degrees C). Cellular uptake and elution of CBA occurred rapidly under in vitro conditions. Uptake of CBA was slightly greater than that of boronophenylalanine (BPA). Following a 3 hr incubation with CBA at a concentration of 106 micrograms B/ml, cell
boron content was 255 micrograms B/10(9) MRA 27 cells, compared to 192 micrograms B/10(9) cells when cells were incubated with BPA at a concentration of 95 micrograms B/ml. In vivo studies initially were carried out using the
Harding-Passey melanoma, which had been implanted intramuscularly (i.m.) into the right flank of BALB/c mice.
Tumors were allowed to grow for 14 days at which time mice were injected intraperitoneally (i.p.) with either CBA or BPA (1.25 mgB/mouse), and were killed 3, 6 and 8 hrs later. CBA attained a low
tumor to blood ratio(1.0-1.4), and the
tumor boron levels ranged from 15.7-26.2 micrograms B/g at 3 hrs and 3.3-19.9 micrograms B/g at 6 hrs. Higher blood and lower
tumor boron levels were observed at all time points with CBA compared to BPA, suggesting that CBA was not taken up selectively by the
melanoma. Similar studies, carried out in rats bearing intra-cerebral
gliomas, failed to reveal detectable amounts of
boron in the
tumor. From the present study, it can be concluded that CBA does not appear to possess the requisite properties to be useful as a
boron delivery agent for BNCT.