Boronated dipeptide borotrimethylglycylphenylalanine as a potential boron carrier in boron neutron capture therapy for malignant brain tumors

A boronated dipeptide, borotrimethylglycylphenylalanine (BGPA), was synthes ized as a possible boron carrier for boron neutron capture therapy (BNCT) f or malignant brain tumors. In vitro, at equal concentrations of B-10 in the extracellular medium, BGPA had the same effect in BNCT as p-boronophenylai anine (BPA). Boron analysis was carried out using prompt gamma -ray spectro metry and track-etch autoradiography. The tumor:btood and tumor:normal brai n B-10 concentration ratios were 8.9 +/-2.1 and 3.0 +/-1.2, respectively, i n rats bearing intracranial C6 gliosarcomas using alpha -particle track aut oradiography. The IC50, i.e. the dose capable of inhibiting the growth of C 6 gliosarcoma cells by 50% after 3 days of incubation, was 5.9 x 10(-3) M B GPA, which is similar to that of 6.4 x 10(-3) M for BPA. The amide bond of BGPA is free from enzymatic attack, since it is protected from hydrolysis b y the presence of a boron atom at the alpha -carbon position of glycine. Th ese results suggest promise for the use of this agent for BNCT of malignant brain tumors. Further preclinical studies of BGBA are warranted, since BGP A has advantages over both BPA and BSH. (C) 2001 by Radiation Research Soci ety.