Synthesis and biological evaluation of new dual agentsfor MRI/BNCT applications

BNCT (Boron Neutron Capture Therapy) is a binary therapy for the treatment of cancer based on the selective uptake of the stable 10B isotope by tumor cells, followed by irradiation with low energy thermal neutrons. In order to be effective BNCT requires 15–30 μg of 10B per g of tumor, therefore, in vivo visualization of 10B distribution is important.1 Thanks to its superb spatial resolution MRI appears to be one of the most appropriate technique to tackle this task. In this work the synthesis and the in vitro and in vivo biological evaluation of a panel of new dual agents for MRI/BNCT applications is reported. Those agents are obtained starting form a versitile dicarbaclosododecaborane intermediate, which assures a high payload of 10B atoms and can be functionalized with different biological vectors and different MRI probes. On one side the carborane cage has been functionalized with lipophilic moieties, like palmityl chains2,3 (AT101) or double-tailed moiety (AT102) or colesterol (AT103) in order to bind the carborane cage to the nanosized vector represented by LDL or liposomes (the real biological vectors). On the other side the carborane has been funtionalized with a Gd-DOTA complex, which allow the boron concentration in cell by means of MRI detection to be quantified.