Tissue Disposition of 5-o-Carboranyluracil — A Novel Agent for the Boron Neutron Capture Therapy of Prostate Cancer.

The carboranyl nucleotides β‐d‐5‐o‐carboranyl‐2′‐deoxyuridine (d‐CDU), 1‐(β‐l‐arabinosyl)‐5‐o‐carboranyluracil (d‐ribo‐CU) and the nucleotide base 5‐o‐carboranyluracil (CU), were developed as sensitizers for boron neutron capture therapy (BNCT). A structure activity study was initiated to determine the agent most suitable for targeting prostate tumors. Cellular accumulation studies were performed using LNCaP human prostate tumor cells, and the respective tumor disposition profiles were investigated in male nude mice bearing LNCaP and 9479 human prostate tumor xenografts in their flanks. d‐CDU achieved high cellular concentrations in LNCaP cells and up to 2.5% of the total cellular compound was recovered in the 5′‐monophosphorylated form. In vivo concentrations of d‐CDU were similar in LNCaP and 9479 tumor xenografts. Studies in 9479 xenografted bearing mice indicated that increasing the number of hydroxyl groups in the sugar moeity of the carboranyl nucleosides corresponded with an increased rate and exte...