IN-VITRO AND IN-VIVO EVALUATION OF O-CARBORANYLALANINE AS A POTENTIALBORON DELIVERY AGENT FOR NEUTRON-CAPTURE THERAPY

o-Carboranylalanine (B10H10C2CH2CHNH2COOH) is a carbonae-containing am ino acid, which has been synthesized as a potential capture agent for boron neutron capture therapy (BNCT) of cancer. The purpose of the pre sent study was to develop a rational approach for the in vitro and in vivo evaluation of boron containing compounds that possibly might be u sed for BNCT. The in vitro uptake of carboranylalanine (CBA) was evalu ated using two cell lines, the human melanoma MRA 27, and the murine H arding-Passey melanoma. Uptake of CBA by MRA 27 cells ranged from 135- 551 mu gB/10(9) cells following 3 hrs incubation with medium containin g 100-113 mu gB/ml and was not reduced by exposing the tumor cells to either rotenone, an inhibitor of electron transport, or by culturing t hem at ambient temperature (similar to 22 degrees C). Cellular uptake and elution of CBA occured rapidly under in vitro conditions. Uptake o f CBA was slightly greater than that of boronophenylalanine (BPA). Fol lowing a 3 hr incubation with BCA at a concentration of 106 mu gB/ml, cell boron content was 255 mu gB/10(9) MRA 27 cells, compared to 192 ( m)u gB/10(9) cells when cells were incubated with BPA at a concentrati on of 95 mu gB/ml. In vivo studies initially were carried out using th e Harding-Passey melanoma which had been implanted intramuscularly (i. p.) into the right flank of BALB/c mice. Tumors were allowed to grow f or 14 days at which time mice were injected intraperitoneally (i.p.) w ith 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 tum or boron levels ranged from 15.7-26.2 mu gB/g at 3 hrs and 3.3-19.9 mu gB/g at 6 hrs. Higher blood and lower tumor boron levels were observe d at all time points with BVA compared to BPA, suggesting that CBA was not taken up selectively by the melanoma. Similar studied carried out in rats bearing intra-cerebral gliomas, failed to reveal detectable a mounts of boron in the tumor. From the present study, it can be conclu ded that CBA does not appear to possess the requisite properties to be useful as a boron delivery agent for BNCT.