Sulfhydryl boron hydride (BSH) (10B enriched) is presently used for
boron neutron capture therapy of
malignant gliomas. BSH must be close to the target cells to be effective in the inactivation of cell proliferation because of the short range of the reaction products (5-9 microns). Clinical experience indicates that BSH is taken up in
gliomas but it is not known to which structures it binds at the cellular level. In vitro tests on monolayer cultured cells have indicated that BSH does not bind, or only shows very weak binding, to single isolated cells. It is possible that BSH accumulates in
tumor regions due to the special conditions in poorly vascularized
tumor tissue, such as low pO2, low extracellular pH, metabolic gradients, and degenerative changes. To test this we incubated three types of multicellular
tumor spheroids with BSH for different times and analyzed both penetration and binding. The spatial distribution of 10B in sections of the spheroids was analyzed by neutron capture autoradiography. We found extensive accumulation of 10B in the central regions of both
glioma and colon
carcinoma spheroids. The accumulation closely followed the pattern of the degenerative changes which were characterized by massive
necrosis in the central regions of the colon
carcinoma spheroids and by a continuously increasing frequency of pyknotic nuclei as a function of depth in the
glioma spheroids. The accumulation of 10B in the prostatic
carcinoma spheroids was much lower. The penetration assay, based on freeze-drying and vapor fixation, showed that BSH penetrated easily since 10B equilibrated within 5-15 min in the studied spheroids. Thus, the low accumulation in the prostatic
carcinoma spheroids was not due to penetration difficulties. The results of the present study on cellular spheroids and the results from previous studies on transplanted
tumors support the observation that BSH penetrates easily into the degenerative
tumor areas and that 10B, for some
tumor types, might accumulate in these regions as a result of the BSH administration.