There are eight specific aims; 1) To develop fully the chemical methodology of synthesizing a variety of different carborane-containing polyamines. 2) To synthesize specific analogues related to putrescine, spermidine, spermine and pentamines with potential tumor DNA-binding properties. 3) To assess their DNA-binding properties in vitro by the displacement of ethidium bromide from DNA. 4) To correlate chemical structure and physiochemical properties with DNA binding activity in order to improve drug design. 5) To determine the in vitro uptake, persistence, and subcellular distribution of boronated polyamines in glioma, melanoma and normal cells. 6) To optimize the hydrophilic/lipophilic properties of compounds in order to enhance tumor cell penetration and DNA binding. 7) To evaluate the in vivo pharmacokinetics and tumor-localizing properties in brain tumor-bearing rats of compounds demonstrating the requisite selectivity and persistence in vitro. 8) To determine the therapeutic efficacy of BNCT in rat models of human glioblastoma and melanoma metastatic to the brain.
