In vivo evaluation of phosphorous-containing derivatives of dodecahydro-closo-dodecaborate for boron neutron capture therapy of gliomas and sarcomas

The in vivo uptake of dodecahydro-closo-dodecaborate derivatives substitute d with phosphate- and bisphosphonate groups was evaluated in two different experimental tumor model systems and compared to other boronated and non-bo ronated compounds. These phosphorous-containing boron clusters may have pot ential for use in boron neutron capture therapy, a chemoradiotherapeutic fo rm of cancer treatment. Using the F98 rat glioma as a brain tumor model in syngeneic Fischer rats, there was selective tumor uptake of the phosphate d erivative with 21.5 mug boron/g tumor versus 5.2 mug/g normal brain and a t umor:blood ratio of 2.7. However, this compound was toxic to test animals a nd lethal at relatively low doses. The uptake of the bisphosphonate by the murine K8 osteosarcoma was similar to 18 mug boron/g tumor with a T:Bl rati o of 7.6 and a tumor:bone ratio of 1.5. This compound was non toxic to the test animals. The results indicate that phosphate- and bisphosphonate deriv atives of dodecahydro-closo-dodecaborate may have potential for BNCT of gli omas and osteosarcomas, respectively.