In vitro determination of uptake and biological efficacy of boronated compounds for neutron capture therapy in the human lung cancer cell line A 549

The purpose of this research was the development of a system for the evaluation of boronated compounds for boron neutron capture therapy (BNCT) in the human lung cancer cell line A 549. The determination of biological efficacy was established by the evaluation of survival curves following irradiation with thermal neutrons. In this research the boronated compounds examined were the boron-containing deoxyribonucleoside CDU-4 and the boron-containing ribonucleoside CN-V-264 and the alpha amino acid LSK 1-38 and the cyclic amino acid m-carboranyl ACBC. The greatest uptake of boron occurred with ACBC followed by LSK 1-38, CN-V-264 and CDU-4 in that order. Toxicity was greatest with the boronated nucleosides; thus, it was necessary to limit these chemicals to a concentration of 2.5 μg/ml. The boronated amino acids revealed lower toxicity, and a higher concentration of 10 μg/ml was feasible. The high cellular uptake of ACBC and lower toxicity makes this the BNCT agent of first choice for future research. The lower cellular uptake of LSK 1-38 and CN-V-264 with very good results make these the BNCT agents of second choice for future research. The high toxicity and low cellular uptake of CDU-4 does leads to a recommendation of this chemical as an agent for future BNCT research as funding is available. A 30 mg ²⁵²Cf source from the Radiochemical Engineering and Development Center at Oak Ridge National Laboratory provided thermal neutrons for this study. A flux of approximately 2 x 10⁸ thermal neutrons/cm²/second was generated by this source in the sample region. All experiments with thermal neutrons plus boronated compounds displayed a greater cancer cell killing effect than control experiments without boronated compounds.