N-benzylpolyamines as vectors of boron and fluorine for cancer therapy andimaging: Synthesis and biological evaluation

Cancer cells have high-affinity polyamine uptake systems with a low stringe ncy for structural features. Putrescine, spermidine, and spermine have, the refore, been considered as potential vectors for the selective accumulation in tumors of therapeutically or diagnostically useful structures and eleme nts. We envisaged N-benzyl derivatives of the polyamines as vectors of B-10 and F-18 for boron neutron capture therapy (BNCT) and tumor imaging by pos itron emission tomography (PET), respectively. In the present work, the syn thesis, transport characteristics, DNA-binding properties, and cytotoxicity of several N-benzyl derivatives of putrescine and spermidine are described . The fluorinated spermidine derivative N-{3-[(4-aminobutyl)aminol]-propyl} [(4-fluorophenyl)methyl]amine (N-1-4-Fbz-spd) may be useful for PET because of its high accumulation in cancer cells via the polyamine transport, syst em. Among the boron-containing benzyl polyamines, N-(4-aminobutyl){[4-(dihy droxyboryl)phenyl]methyl}amine (4-Bbz-put) and N-{3-[(4-aminobutyl)amino]pr opyl}{[4-(dihydroxyboryl)phenyl]methyl}amine (4-Bbz-spd) should be suitable for BNCT, because their accumulation in B16 melanoma cells was more effici ent than that of borocaptate and borophenylalanine, two reference compounds used in BNCT.