Intracellular distribution of various boron compounds for use in boron neutron capture therapy.

The neutron capture reaction in boron (10B(n, alpha)7Li) generates two short-range particles with high linear energy transfer. The effect of neutron capture therapy depends on the selective localization of 10B atoms in target cells. The determination of the distribution of boron compounds in cancer cells at the subcellular level is required for the understanding of the effect of this treatment. The monomeric sulfhydryl borane (BSH) compound has been used clinically in Japan and preclinically in the U.S.A. Recently, new compounds have been developed: a dimeric sulfhydryl borane (BSSB), a boronophenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). This study demonstrates that the porphyrin complexes (BOPP and VCDP) are more cytotoxic than the other three compounds to the rat 9L gliosarcoma cell line. Using atomic absorption spectrophotometry to determine boron content for cellular uptake studies of these agents, we found that of the five compounds tested BOPP (25 microM) exposure resulted in the greatest boron uptake averaging 305 ng B/10(6) cells. BSSB (500 microM) was second averaging 93 ng B/10(6) cells, BSH (500 microM) third averaging 62 ng B/10(6) cells, VCDP (25 microM) fourth averaging 58 ng B/10(6) cells, and BPA (500 microM) fifth averaging 7.4 ng B/10(6) cells. Data on the distribution of boron in the nuclei, mitochondria, lysosomes, microsomes, and cytosomes of 9L cells are also presented.